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Pierce D Nunley,1 Vikas V Patel,2 Douglas G Orndorff,3 William F Lavelle,4 Jon E Block,5 Fred H Geisler6 1Spine Institute of Louisiana, Shreveport, LA, 2The Spine Center, University of Colorado Hospital, Denver, CO, 3Spine Colorado, Mercy Regional Hospital, Durango, CO, 4Upstate Bone and Joint Center, East Syracuse, NY, 5Independent Consultant, San Francisco, CA, 6Independent Consultant, Chicago, IL, USA Background: Lumbar spinal stenosis is the most common indication for spine surgery in older adults. Interspinous process decompression (IPD) using a stand-alone spacer that functions as an extension blocker offers a minimally invasive treatment option for intermittent neurogenic claudication associated with spinal stenosis.Methods: This study evaluated the 5-year clinical outcomes for IPD (Superion®) from a randomized controlled US Food and Drug Administration (FDA) noninferiority trial. Outcomes included Zurich Claudication Questionnaire (ZCQ) symptom severity (ss), physical function (pf), and patient satisfaction (ps) subdomains, leg and back pain visual analog scale (VAS), and Oswestry Disability Index (ODI).Results: At 5 years, 84% of patients (74 of 88) demonstrated clinical success on at least two of three ZCQ domains. Individual ZCQ domain success rates were 75% (66 of 88), 81% (71 of 88), and 90% (79 of 88) for ZCQss, ZCQpf, and ZCQps, respectively. Leg and back pain success rates were 80% (68 of 85) and 65% (55 of 85), respectively, and the success rate for ODI was 65% (57 of 88). Percentage improvements over baseline were 42%, 39%, 75%, 66%, and 58% for ZCQss, ZCQpf, leg and back pain VAS, and ODI, respectively (all P1.0; all P

Vikas V Patel,1 Pierce D Nunley,2 Peter G Whang,3 Thomas R Haley,4 W Daniel Bradley,5 Raphael P Davis,6 Jon E Block,7 Fred H Geisler8 1The Spine Center, University of Colorado Hospital, Denver, CO, 2Spine Institute of Louisiana, Shreveport, LA, 3Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, 4Performance Spine and Sports Physicians, PC, Pottstown, PA, 5Texas Back Institute, Denton, TX, 6Department of Neurological Surgery, Stony Brook Medicine, Stony Brook, NY, 7Jon Block, Ph.D. San Francisco, CA, 8McLaren Hospital, Petoskey, MI, USA Purpose: This report provides the 3-year clinical outcomes from the randomized, controlled US Food and Drug Administration Investigational Device Exemption trial of the Superion® for the treatment of moderate degenerative lumbar spinal stenosis. Patients and methods: The Superion® was evaluated in the treatment of subjects aged 45 years or older suffering from symptoms of intermittent neurogenic claudication, secondary to a confirmed diagnosis of moderate degenerative lumbar spinal stenosis at one or two contiguous levels from L1 to L5. Patients were treated between June 2008 and December 2011 at 31 investigational sites. Three hundred ninety-one subjects were included in the randomized study group consisting of 190 Superion® and 201 X-STOP® control subjects. The primary composite endpoint was individual patient success based on four components: improvement in two of three domains of the Zurich Claudication Questionnaire, no reoperations at the index level, no major implant/procedure-related complications, and no clinically significant confounding treatments. Results: At 3 years, the proportion of subjects achieving the primary composite endpoint was greater for Superion® (63/120, 52.5%) than for X-STOP® (49/129, 38.0%) (P=0.023) and the corresponding success rates exceeded 80% for each of the individual components of the primary endpoint in the Superion® group (range: 81%–91%). Improvements in back and leg pain severity as well as back- and disease-specific functional outcomes were also maintained through 36 months. Conclusion: The 3-year outcomes from this randomized controlled trial demonstrate durable clinical improvement consistently across all clinical outcomes for the Superion® in the treatment of patients with moderate degenerative lumbar spinal stenosis. Keywords: InterSpinous Spacer, lumbar spinal stenosis, Superion®, neurogenic claudication

STUDY DESIGN: A basic science study monitoring changes in the curvature of hand contoured commercially pure titanium (CPTi), titanium-aluminum-vanadium alloy (Ti-6Al-4V), and stainless steel (SS) rods maintained at different temperature conditions. OBJECTIVE: To quantify changes in rod-shape at temperatures representative of those used in clinical practice. SUMMARY OF BACKGROUND DATA: The shape of implanted rods can be displaced due to thermo-mechanical properties of the materials. Warmer temperatures likely initiate this effect. A study of shape loss characteristics of various rod implants may help eliminate undesirable outcomes caused by shape displacement. METHODS: Three different types of rods (CPTi, SS, and Ti-6Al-4V) were hand contoured and then maintained in one of following temperature conditions for 35 days: (1) room temperature (20 °C-25 °C) without autoclaving before contouring; (2) preliminary autoclaving (1, 5, 10, 20 cycles) at 135.0 °C ± 2 °C before contouring followed by body temperature (37.2 °C ± 2 °C). Each rod was 5 mm in diameter and 200 mm long. The rods were mounted over graph paper in fixed positions and photographed to measure displacement of the tip as a function of the curvature. RESULTS.: Statistically significant shape loss of the rods manufactured from all the tested materials was found. The hand contoured CPTi rods displayed considerably higher loss of curvature over time than Ti-6Al-4V and SS rods at all tested temperature conditions. Preliminary autoclaving at 135 °C before contouring tended to amplify this effect, in particular 1 cycle of autoclaving. If the number of preliminary autoclaving cycles was higher (5-10), a tendency of decrease of shape loss effect was observed in Ti-6Al-4V and CPTi rods. CONCLUSION: The shape of the hand contoured CPTi rods was the least stable of the rods across all applied temperature conditions. The SS and Ti-6Al-4V rods were more stable than CPTi rods. Autoclaving before handcontouring tended to increase rods' shape loss. [ABSTRACT FROM AUTHOR]

Atrial fibrillation is the most common clinical cardiac arrhythmia. It is often initiated by ectopic beats arising from the pulmonary veins and atria. While pulmonary vein myocytes most likely contribute to atrial ectopic beats initiating atrial fibrillation, emerging evidence suggests the existence of other cell populations that may also contribute to atrial arrhythmias. In addition to sinus node-like and intestinal Cajal-like cells, we recently characterized a novel, melanocyte-like cell population in murine and human hearts that may contribute to atrial arrhythmogenic triggers in mice. Murine cardiac melanocyte-like cells are electrically excitable, and express adrenergic and muscarinic receptors. Adult mice lacking the gene encoding dopachrome tautomerase (Dct) are susceptible to atrial arrhythmias, and Dct is expressed by both murine and human cardiac melanocytes. While Dct-expressing cells are present in human hearts in regions from which atrial arrhythmias often arise, the contribution of these cells to clinical atrial arrhythmias remains to be determined. [ABSTRACT FROM AUTHOR]

Proper mechanical and electrical coupling of cardiomyocytes is crucial for normal propagation of the electrical impulse throughout the working myocardium.Various proteins on the surface of cardiomyocytes are responsible for the integration of structural information and cell-cell communication. Increasing evidence from diseased myocardium and animal models indicates that alteration in electrical coupling via gap junctions is a critical determinant in the development of an arrhythmogenic substrate. What is less clear is how gap junctions are maintained and regulated in the working myocardium. In this review, we present data from human disease and animal models that support the idea that cell adhesion proteins regulate the stability of the gap junction protein, connexin. [ABSTRACT FROM AUTHOR]

Various navigation systems are available to aid pedicle screw placement. The O-arm replaces the need for fluoroscopy and generates a 3-dimensional volumetric dataset that can be viewed as transverse, coronal, and sagittal images of the spine, similar to computed tomography (CT) scanning. The dataset can be downloaded to the Stealth system (Medtronic Navigation, Louisville, Colorado) for real-time intraoperative navigation.The main objectives of the current study were to assess (1) accuracy of pedicle screw placement using the O-arm/Stealth system, and (2) time for draping, positioning of the O-arm, and screw placement. Of 188 screws (25 patients), 116 had adequate images for analysis. The average time for O-arm draping was 3.5 minutes. Initial O-arm positioning was 6.1 minutes, and final positioning was 4.9 minutes. Mean time for screw placement, including O-arm draping and positioning and array attachment, was 8.1 minutes per screw. Mean time for screw placement alone was 5.9 minutes per screw. Screw placements on final O-arm images were on average 3.14 mm deeper than on the snapshot navigation images. Three screws (2.6%) breached the medial cortex, and 3 screws (2.6%) were misaligned and did not follow the pilot hole trajectory.The use of the O-arm/Stealth system was associated with a low rate of pedicle screw misalignment. The time to place screws was less than previously reported with CT navigation, but longer than conventional techniques. It is important to be aware of the potential discrepancy between snapshot navigation images and actual screw placement on final O-arm images. Our findings suggest that final screw positions may be deeper than awl positions appear on navigation images. [ABSTRACT FROM AUTHOR]

Case: A rarely reported complication with sacroiliac joint fusion (SJF) is an iatrogenic injury to the superior gluteal artery (SGA). This case series includes 3 cases which had a suspected injury to the SGA. Case 1 describes how hemostasis achieved with exploration of the wound followed by embolization by interventional radiology (IR). In Case 2, electrocautery, hemostatic agents, and pressure were used with success. Case 3 highlights the use of IR as the initial method for controlling bleeding., Conclusion: This report describes a rare complication during SJF and provides an algorithm to help guide surgeons in decision making., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C438)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background Context: Failure to fuse following anterior cervical discectomy and fusion (ACDF) may result in symptomatic pseudoarthrosis. Traditional diagnosis involves computerized tomography to detect bridging bone and/or flexion-extension radiographs to assess whether segmental motion is above specific thresholds; however, there are currently no well-validated diagnostic tests. We propose a biomechanically rational approach to achieve a reliable diagnostic test for pseudoarthrosis., Purpose: Develop and test a biomechanically based approach to the diagnosis of pseudoarthrosis., Study Design: Literature review, development of theory, re-analysis of a previously published study with surgical exploration as the gold-standard, and retrospective analysis of pooled studies to understand time to fusion., Methods: Fully automated methods were used to measure disc space strains (change in disc space height divided by initial height). Measurement error combined with the reported failure strain of trabecular bone led to a proposed strain threshold for diagnosis of pseudoarthrosis following ACDF. We reanalyzed previously reported flexion-extension radiographs for asymptomatic volunteers to assess whether flexion-extension radiographs, in the absence of fusion surgery, can be expected to provide sufficient stress on motion segments to allow for reliable strain-based fusion assessment. The sensitivity and specificity of strain- and rotation-based pseudoarthrosis diagnosis were assessed by reanalysis of previously reported post-ACDF flexion-extension radiographs, where intraoperative fusion assessments were also available. Finally, we assessed changes in strain over time using 9,869 flexion-extension radiographs obtained 6 weeks to 84 months post-ACDF surgery from 1,369 patients., Results: The estimated error in automated measurement of disc space strain from radiographs was approximately 3%, and the reported failure strain of bridging bone was less than 2.5%. On that basis, we propose a 5% strain threshold for pseudoarthrosis diagnosis. Reanalysis of a study in which intraoperative fusion assessments were available revealed 67% sensitivity and 82% specificity for strain-based diagnosis of pseudoarthrosis, which was comparable to rotation-based diagnosis. Analysis of post-ACDF flexion-extension radiographs revealed rapid strain reduction for up to 24 months, followed by a slower decrease for up to 84 months. When rotation is less than 2 degrees, the strain-based diagnosis differed from the rotation-based diagnosis in approximately 14% of the cases., Conclusions: We propose steps for standardizing diagnosis of pseudoarthrosis based on the failure strain of bone, measurement error, and retrospective data. These steps include obtaining high-quality flexion-extension studies, the application of proposed diagnostic thresholds, and the use of image stabilization for conclusive diagnosis, when motion is near thresholds. The necessity for an accurate diagnosis with minimal radiation exposure underscores the need for further optimization and standardization in diagnosing pseudoarthrosis following ACDF surgery., Clinical Significance: In a symptomatic postspine fusion patient, it is important to diagnose or rule-out pseudoarthrosis. There are currently no well-validated diagnostic tests for this condition. Incorporating strain-based intervertebral motion analysis into the diagnosis could lead to a standardized and validated test for detecting spine pseudoarthrosis., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Men who have sex with men (MSM) and female sex workers (FSW) are increasingly and disproportionately impacted by HIV in sub-Saharan Africa, yet current PrEP care models in this region are not optimized for these communities. Limited data exist describing experiences and preferences of MSM and FSW with respect to accessing and using PrEP., Methods: We conducted qualitative, semi-structured interviews with MSM and FSW recruited from three health centers and seven community organizations in Kigali, Rwanda. Data were analyzed using a mixed deductive and inductive approach to describe key themes related to initiating and adhering to PrEP., Results: Participants included 18 MSM and 14 FSW; 12 were using PrEP at the time of interview, 9 had previously used PrEP, and 11 had never used it. Participants highlighted the central role of their social networks as key sources of information about and support for PrEP use, and described a strong motivation to use PrEP as a way to protect both themselves and their communities from HIV. While stigma and discrimination were pervasive, these were experienced differently by MSM and FSW. Participants suggested community access points that allowed more discreet and less frequent contact with health care workers as important and desired strategies to improve engagement., Conclusions: These findings suggest that leveraging community resources for disseminating information about HIV prevention and delivering PrEP could contribute to successful implementation of PrEP for MSM and FSW in Rwanda and other settings in SSA., Competing Interests: Competing interests: The authors have no conflicts of interest or competing interests to declare.

Introduction: Community-based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre-exposure prophylaxis (PrEP). Within individuals, one can assess exposure and outcome variables repeatedly and with increased certainty regarding temporal ordering. This cohort study examined the association of several risk factors with subsequent HIV seroconversion., Methods: We report data from a 4-year study (2017-2022) of 6059 HIV seronegative sexual and gender minority individuals who have sex with men who had indications for-, but were not using-, PrEP at enrolment. Participants completed repeat exposure assessments and self-collection of biospecimens for HIV testing. We examined the roles of race and ethnicity, socio-economic status, methamphetamine use and PrEP uptake over the course of follow-up in relation to HIV seroconversion., Results: Over 4 years, 303 of the participants seroconverted across 18,421 person-years (incidence rate = 1.64 [95% CI: 1.59-1.70] per 100 person-years). In multivariable discrete-time survival analysis, factors independently associated with elevated HIV seroconversion risk included being Black/African American (adjusted risk ratio [aRR]: 2.44, 1.79-3.28), Hispanic/Latinx (1.53, 1.19-1.96), housing instability (1.58, 1.22-2.05) and past year methamphetamine use (3.82, 2.74-5.33). Conversely, time since study enrolment (24 vs. 12 months, 0.67, 0.51-0.87; 36 months, 0.60, 0.45-0.80; 48 months, 0.48, 0.35-0.66) and higher education (master's degree or higher vs. less than or equal to high school, 0.36, 0.17-0.66) were associated with reduced seroconversion risk. Compared to non-PrEP users in the past 2 years without a current clinical indication, those who started PrEP but then discontinued had higher seroconversion risk, irrespective of clinical indication (3.23, 1.74-6.46) or lack thereof (4.30, 1.85-9.88). However, those who initiated PrEP in the past year (0.14, 0.04-0.39) or persistently used PrEP in the past 2 years (0.33, 0.14-0.74) had a lower risk of seroconversion. Of all HIV seroconversions observed during follow-up assessments (12, 24, 36 and 48 months), methamphetamine was reported in the 12 months prior 128 (42.2%) times (overall)., Conclusions: Interventions that acknowledge race and ethnicity, economic variables such as education and housing instability, and methamphetamine use are critically needed. Not only are interventions to engage individuals in PrEP care needed, but those that retain them, and re-engage those who may fall out of care are essential, given the exceptionally high risk of seroconversion in these groups., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Methamphetamine use is on the rise among sexual and gender minority people who have sex with men (SGMSM), escalating their HIV risk. Despite pre-exposure prophylaxis (PrEP) being an effective biomedical HIV prevention tool, its uptake in relation to methamphetamine use patterns in SGMSM has not been studied. In a U.S. cohort study from 2017 to 2022, 6,253 HIV-negative SGMSM indicated for but not using PrEP were followed for four years. Methamphetamine use was categorized (i.e., newly initiated, persistently used, never used, used but quit), and PrEP uptake assessed using generalized estimating equation (GEE), adjusted for attrition. Participants had a median age of 29, with 51.9% White, 11.1% Black, 24.5% Latinx, and 12.5% other races/ethnicities. Over the four years, PrEP use increased from 16.3 to 27.2%. GEE models identified risk factors including housing instability and food insecurity. In contrast, older age, health insurance, clinical indications, and prior PrEP use increased uptake. Notably, Latinx participants were more likely to use PrEP than Whites. Regarding methamphetamine use, those who newly initiated it were more likely to use PrEP compared to non-users. However, those who quit methamphetamine and those who persistently used it had PrEP usage rates comparable to those of non-users. Though PrEP uptake increased, it remained low in SGMSM. Methamphetamine use was associated with PrEP uptake. Healthcare providers should assess methamphetamine use for harm reduction. Prioritizing younger, uninsured SGMSM and addressing basic needs can enhance PrEP uptake and reduce HIV vulnerabilities., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: PrEP uptake among Black and Latino gay, bisexual, and other men who have sex with men (GBM) remains low in the United States. The design and implementation of PrEP delivery programs that incorporate the preferences of Black and Latino GBM may overcome barriers to uptake. We aimed to identify preferences for PrEP care among high-priority GBM in the U.S. with a large discrete choice experiment., Methods: We conducted two discreet choice experiments (DCE) to elicit care preferences for (1) Starting PrEP and (2) Continuing PrEP care among GBM clinically indicated for PrEP. The DCE web-based survey was nested in a longitudinal cohort study of GBM in the U.S., implemented with video and audio directions among 16-49 year-old participants, not using PrEP, and verified to be HIV-negative. All participants were presented with 16 choice sets, with choices determined by BLGBM and PrEP implementation stakeholders. We calculated overall utility scores and relative importance and used latent class analyses (LCA) to identify classes within the Starting and Continuing PrEP DCE. Multivariable analysis was performed to identify factors associated with class membership., Findings: Among 1514 participants, mean age was 32 years; 46·5% identified as Latino, 21·4% Black, and 25·2 White; 37·5% had an income less than USD $20,000. Two latent classes were identified for Starting PrEP: Class 1 (n=431 [28·5%]) was driven by preference for more traditional in-person care, and Class 2 (n=1083 [71·5%]) preferred flexible care options and on-demand PrEP. In a multivariable model, having a sexual health doctor (adjusted OR 0·7, CI 0·5, 0·9), having a primary care provider (OR 0·7,CI 0·5, 0·9, p= 0·023), and concerns over PrEP side effects (OR 1·1, CI 1·0,1·2, p= 0·003) were all associated with class membership., Interpretation: The different preferences identified for PrEP care indicate the need for diverse care and formulation choices to improve PrEP uptake and persistence. Addressing these preferences and understanding the factors that shape them can inform the implementation of programs that increase PrEP uptake.

High-resolution manometry (HRM) is used to evaluate the esophageal motor function. Unfortunately, there are times when testing cannot be performed accurately. Our study aimed to quantify the occurrence of failed HRM and identify the associated risk factors. HRM tests were retrospectively collected between September 2021 and August 2022. HRM reports that could not be interpreted based on standard HRM protocol as per Chicago guidelines were classified as failed tests. Information reviewed included testing indications, patient demographics, previous medical/symptom history, and follow-up testing for failed HRM. We then compared patients with successful vs. unsuccessful HRM based on our pre-specified factors. 152 HRM tests were performed, of which 28 tests (18%) were unsuccessful. Factors associated with failed manometry included a history of nausea/vomiting, dyspepsia, and achalasia. Patients who were unable to tolerate the probe during testing were more likely to have a history of dyspepsia (OR 20.3, p = < 0.001) and/or nausea/vomiting (OR 13.8, p = < 0.001). A history of achalasia was found to have an odds ratio of 13.2 when examining failure because of curling of the manometry catheter (p = 0.012). All seven patients who had repeat HRM with endoscopic placement were successful in obtaining diagnostic information. There are two groups that have risk factors for unsuccessful HRM testing. A history of nausea/vomiting and dyspepsia symptoms were associated with being unable to tolerate the manometry probe. The second group comprises patients with a history of achalasia in whom probe curling is more common. Future research targeting these risk factors may minimize diagnostic and treatment delays., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the US, sexual and gender minority populations are disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) is a key prevention method, but its effectiveness relies on consistent usage. Our four-year national cohort study explored PrEP discontinuation among sexual and gender minority people who initiated PrEP. We found a high annual rate of discontinuation (35-40 percent) after PrEP initiation. Multivariable analysis with 6,410 person-years identified housing instability and prior history of PrEP discontinuation as predictors of discontinuation. Conversely, older age, clinical indication for PrEP, and having health insurance were associated with ongoing PrEP use. To promote sustained PrEP use, strategies should focus on supporting those at high risk for discontinuation, such as younger people, those without stable housing or health insurance, and prior PrEP discontinuers.

Introduction: Pre-exposure Prophylaxis (PrEP) is a daily pill aimed at reducing HIV transmission risk when taken as prescribed. It's highly recommended for high-risk Men who have sex with Men (MSM). This study aimed to assess PrEP awareness and willingness to use it among Rwandan MSM, a critical aspect given PrEP's proven effectiveness. The findings are expected to inform policy decisions and further advance the implementation of PrEP strategies., Methods: This is a cross-sectional study design that utilized a web-based survey conducted between April and June 2019 to assess awareness and willingness to use PrEP among sexually active MSM in Rwanda. A snowball sampling technique was used to recruit participants via social media such as WhatsApp and e-mail. Eligibility criteria included being sexually active, aged ≥18 years, self-identifying as MSM, residing in Rwanda, self-reported engagement in receptive or insertive anal sex in the last 12 months, and self-reported HIV-negative serostatus. We assessed two primary outcomes: PrEP awareness (having ever heard of PrEP) and willingness to use PrEP within one month of completing the survey. Multivariable logistic regression was performed to identify participant characteristics associated with PrEP awareness and willingness to use it., Results: Out of 521 participants, the majority (73%) demonstrated awareness of PrEP. Factors linked to PrEP awareness included residing outside the capital, Kigali, being in the 18-29 age group, having higher education levels, perceiving a benefit from PrEP, and engaging in vaginal sex with a woman while using a condom in the last year. Additionally, 96% of participants expressed a strong willingness to use PrEP., Conclusion: Rwandan MSM exhibits a high level of PrEP awareness, notably associated with factors like location, age, education, perceived benefits, and condom use. The study also revealed a strong willingness to use PrEP, indicating promising prospects for its adoption among this group. These findings highlight the need for targeted awareness campaigns, personalized interventions, and comprehensive sexual health education to promote PrEP adoption and strengthen HIV prevention efforts among Rwandan MSM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Munyaneza, Patel, Gutierrez, Shi, Muhoza, Kubwimana, Ross, Nsereko, Murenzi, Nyirazinyoye, Mutesa, Anastos and Adedimeji.)

Introduction: Surface roughness of the crowns is dependent on the pattern material used for the making as well as the procedure of investing. The study was aimed to examine the impact of various pattern materials and investment procedures on the surface roughness of nickel-chromium alloy raw castings., Materials and Methods: An in-vitro study was piloted at a tertiary care hospital. Eighty samples of inlay wax and pattern resin were divided equally. They were invested in phosphate-bonded investment material and kept under normal atmospheric pressure as well as invested under a pressure of 3 bars. The surface roughness was calculated with a Profilometer. The values obtained were compared using statistical tools keeping P < 0.05 as significant., Results: Lowest surface roughness was seen for the wax pattern invested under positive pressure. While the highest was seen for the resin patterns invested at room pressure. A significant variance between the wax 1 and wax 2 ( P < 0.01); as well as between the wax 2 vs. Resin 2 specimens ( P < 0.01) was noted., Conclusions: Wax patterns can be suggested as the material and method of choice because they showed the least amount of surface roughness when placed under pressure. Resin patterns when invested under pressure can also be suggested as an alternate as they also exhibited similar surface roughness as that of the wax., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Lesbian, gay, bisexual, transgender, queer, and other sexual and gender minority (LGBTQ +) individuals experience bias in healthcare with 1 in 6 LGBTQ + adults avoiding healthcare due to anticipated discrimination and overall report poorer health status compared to heterosexual and cisgendered peers. The Society of General Internal Medicine (SGIM) is a leading organization representing academic physicians and recognizes that significant physical and mental health inequities exist among LGBTQ + communities. As such, SGIM sees its role in improving LGBTQ + patient health through structural change, starting at the national policy level all the way to encouraging change in individual provider bias and personal actions. SGIM endorses a series of recommendations for policy priorities, research and data collection standards, and institutional policy changes as well as community engagement and individual practices to reduce bias and improve the well-being and health of LGBTQ + patients., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Community-based organizations (CBOs) deliver services in culturally-responsive ways, and could effectively partner with health centers to deliver HIV pre-exposure prophylaxis (PrEP) to Latino men who have sex with men (LMSM). However, few such models exist. We conducted a planning study in collaboration with three CBOs serving LMSM to identify optimal PrEP delivery strategies for health centers and CBOs to implement jointly. We established a Community Expert Panel (CEP) of eight client-facing CBO and health center staff. Over 6 months, the panel met monthly to identify collaborative strategies for PrEP delivery, using a modified Delphi method consisting of the following steps: (1) brainstorming strategies; (2) rating strategies on acceptability, appropriateness and feasibility; (3) review of data from qualitative focus group discussions with CBO clients; and (4) final strategy selection. The panel initially identified 25 potential strategies spread across three categories: improving communication between health centers and CBOs; using low-barrier PrEP options (e.g. telemedicine), and developing locally-relevant, culturally-sensitive outreach materials. Focus groups with CBO clients highlighted a desire for flexible options for PrEP-related care and emphasized trust in CBOs. The final package of strategies consisted of: (1) a web-based referral tool; (2) telemedicine appointments; (3) geographically-convenient options for lab specimen collection; (4) tailored print and social media; and (5) regular coaching sessions with CBO staff. Through a community-engaged process, we identified a package of PrEP delivery strategies that CBOs and health centers can implement in partnership, which have the potential to overcome barriers to PrEP for LMSM., (© 2023. The Author(s).)

Latinx sexual minority men (LSMM) face multilevel barriers to accessing HIV pre-exposure prophylaxis (PrEP). To address these barriers, we designed and implemented community-based organization (CBO)-PrEP, a collaborative community-based telehealth PrEP program for LSMM. We designed this PrEP delivery program through a collaborative process involving staff from local CBOs and a primary care-based HIV prevention program. Staff met weekly over a 3-month period to establish protocols for referrals, obtaining insurance coverage, and navigation to appointments and laboratory testing. To assess feasibility, we extracted electronic medical record data including demographics and clinical outcomes of PrEP care. Between December 2020 and May 2023, 102 individuals were referred to CBO-PrEP of which 85 had Hispanic/Latino as their ethnicity in their medical records; out of 102 individuals, 72 (70.6%) were scheduled for an initial appointment. Out of 72 individuals scheduled for an appointment, 58 (80.6%) were seen by a health care provider a median of 7.5 days after referral [interquartile range (IQR), 2-19]; 48 (82.6%) of initial appointments were through telemedicine, 10 (17.2%) were seen in person. Of the 48 patients who had a telehealth appointment, 36 (75%) underwent initial laboratory testing and 42 (87.5) were prescribed PrEP; all 10 patients who were seen in person underwent laboratory testing and were prescribed PrEP. PrEP prescriptions were received in a median of 17.5 days (IQR 4.5-33.5) after referral. CBO-PrEP successfully engaged LSMM, a population that is often hard to reach. Expanding collaborative approaches with CBOs could have a significant impact on improving PrEP uptake for LSMM and other priority populations.

Low back pain is a multidimensional disorder that can originate from a variety of pain generators, including the sacroiliac (SI) joint. Although the Oswestry Disability Index (ODI) is often used in SI joint treatment studies, the effects of the SI joint on functional disability are likely different from those of other low back pain generators. Thus, we developed the Denver SI Joint Questionnaire (DSIJQ) and performed validation testing in patients (n=24) with SI joint-specific pain at baseline, +2 weeks, and +6 months. Psychometric analyses included test-retest reliability, internal consistency, content validity, convergent criterion validity, divergent criterion validity, and responsiveness. The DSIJQ showed good test-retest reliability (intraclass correlation coefficient=0.87), internal consistency (Cronbach's alpha=0.842), content validity (<30% floor/ceiling effects), convergent criterion validity ( r =0.89; P <.001), and divergent criterion validity ( r =-0.33; P =.12). The DSIJQ was correlated with performance on two physical function tests: Timed Upand-Go ( r =0.53; P =.008) and 5 Minute Walk ( r =-0.52; P =.009). The DSIJQ showed better responsiveness than the ODI (standardized response mean and effect size, 1.14 and 1.45 for DSIJQ and 0.75 and 0.81 for ODI). Overall, the DSIJQ performed well on all psychometrics. Importantly, we validated the DSIJQ with patients' ability to complete two tests of physical functioning. Moreover, the DSIJQ was more sensitive to changes in SI joint disability than the ODI. These psychometrics suggest the DSIJQ is appropriate for evaluating SI joint disability and detecting changes in disability after targeted SI joint treatment. [ Orthopedics . 2023;46(6):345-351.].

The high incidence of HIV among US Black sexual minority men is a public health crisis that pre-exposure prophylaxis (PrEP) for HIV can help address. Public health campaigns, which often include pictures of Black sexual minority men alongside PrEP-related messaging, have been developed to encourage PrEP awareness and uptake. However, the acceptability of the messaging within these campaigns among Black sexual minority men is unclear. We conducted four focus groups with 18 HIV-negative Black sexual minority men in Washington, DC to explore their perspectives regarding promotional messaging (textual elements) in PrEP visual advertisements, including their reactions to three large-scale public health campaigns. Primary themes included: (1) the need for additional information about PrEP, (2) preference for slogan simplicity, (3) the desire to normalise PrEP use, and (4) mixed views on the inclusion of condoms. Results indicated that the messaging in current PrEP visual advertisements may not sufficiently address Black sexual minority men's questions about PrEP. Providing basic PrEP information and methods to access more information; using simple, unambiguous language; presenting PrEP use in a destigmatising, normalising fashion; and conveying the relevance of condoms if included in the advertisement could help increase the acceptability of future PrEP advertising among Black sexual minority men.

Online outreach may be an important strategy to reach Indian gender minority (GM) populations for HIV testing. However, little is known about Indian GM populations reached online who are sexually active and their HIV testing behaviors. We conducted a secondary analysis of an India wide online cross-sectional survey to assess HIV testing and identify associated factors. The 467 GM respondents identified their gender as transgender women (29.6%), Hijra (5.1%), intersex (37%), or gender non-binary (28.3%). Overall, almost half (47.5%) had never been tested for HIV; among respondents having condomless anal sex, half (50%) reported never testing for HIV. A decreased odds of ever HIV testing was associated with being unsure how to access free testing (compared to being easy; AOR = 0.36, 95%CI 0.20, 0.63) and unaware of comfortable testing sites (AOR = 0.32, 95% CI 0.20, 0.63). Increased odds of testing were associated with identifying as Hijra (compared to transgender women; AOR = 4.07, 95%CI 1.18-16.92) and disclosing sexual behaviors to a doctor (AOR = 3.20, 95% CI 1.91, 5.46). In this GM sample recruited online, HIV testing rates were low. Online interventions are needed to engage individuals with diverse GM identities in India for linkage to accessible and acceptable HIV testing options., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Young Black and Latino men who have sex with men (YBLMSM) have the highest rates of new HIV infections in the USA and use PrEP at lower rates than White MSM., Objective: To explore YBLMSM's perspectives and experiences of PrEP use to identify factors enabling or impeding uptake., Design: Qualitative study using semi-structured interviews conducted between August 2015 and April 2016., Participants: Black and Latino MSM, 18-20 years of age, who live, socialize, or work in the Bronx, and were fluent in English or Spanish., Approach: We used a thematic analysis to identify themes related to not taking PrEP and PrEP uptake., Key Results: Half the participants (n = 9) were currently using PrEP, a majority had Medicaid (n = 13), all reported having a PCP, all identified English as their primary language (n = 15), and all identified as gay. Salient themes included concerns over-side effects, stigma related to HIV and sexuality, mistrust of medical providers, provider's refusal to prescribe PrEP, and insurance and cost., Conclusions: Modifiable barriers for PrEP uptake and persistence were reported by most participants, with an emphasis on PrEP misinformation and the pervasiveness of intersectional stigma, providers' low awareness, and hesitant attitudes towards PrEP and barriers created by insurance companies. Supportive infrastructures for PrEP providers and patients are needed., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

In recent decades, the increased incidence of cardiovascular disease (CVD) mortality among young adults has raised concerns. Although clinical manifestations of CVD typically occur later in life, the underlying pathological processes emerge early on. This review article summarizes the association between vitamin B deficiency-induced hyperhomocysteinemia and subclinical atherosclerosis in adolescents. Numerous studies have demonstrated that elevated homocysteine levels are an independent risk factor for endothelial dysfunction (ED) and arterial stiffness, which are key contributors to CVD. Notably, vitamin B deficiency, particularly in vitamin B9 and vitamin B12, emerges as a significant factor in childhood hyperhomocysteinemia, initiating the development of subclinical atherosclerosis in early life. A comprehensive review of relevant literature from prominent bibliographic databases, including PubMed/MEDLINE, PubMed Central, Google Scholar, and Cochrane, was performed. Four cross-sectional studies focusing on homocysteine levels as an exposure variable and markers of atherosclerosis as outcome measures were included and reviewed as part of our analysis. The reviewed studies demonstrate a positive correlation between homocysteine levels and markers of atherosclerosis, including increased carotid intima-media thickness (CIMT) and ED. Mainly, adolescents with vitamin B12 deficiency exhibit a significant positive correlation between homocysteine levels and CIMT. These findings underscore the potential of hyperhomocysteinemia as an early marker for detecting subclinical atherosclerosis in adolescents with vitamin B deficiency. Despite limited research in this area, recognizing the importance of early detection and management of subclinical atherosclerosis in adolescents can help mitigate the risk of severe cardiovascular events such as myocardial infarction and stroke in young adulthood., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Shirode et al.)

Disparities in HIV incidence and PrEP uptake suggest a need to prioritize Black sexual minority men (SMM) in PrEP social marketing initiatives. However, images linking Black SMM to HIV and PrEP may inadvertently reinforce stigma. We examined HIV-negative/status-unknown Black SMM's responses to targeted PrEP advertisements using mixed methods, including an experiment embedded in a longitudinal online survey (Time 1: n = 96; Time 2 [eight weeks]: n = 73) and four focus groups (n = 18). The full factorial experiment included between-groups and within-subjects comparisons. For between-groups comparisons, each participant was randomly assigned to view one of 12 advertisements, which varied by couple composition (Black SMM couple/Black heterosexual couple/multiple diverse couples/no couples) and campaign (PrEPare for the Possibilities/PlaySure/PrEP4Love). We examined couple composition, campaign, and interaction effects on: advertisement judgments (Time 1), PrEP stigma (Time 1), PrEP motivation (Times 1 and 2), and PrEP behavior (Time 2). For within-subjects comparisons, each participant viewed all 12 advertisements, and we examined couple composition, campaign, and interaction effects on advertisement judgments (Time 2). Focus group participants discussed advertising preferences and responded to the same set of advertisements. For between-groups and within-subjects comparisons, we found significant couple composition effects but no or limited campaign and interaction effects on advertisement judgments. Advertisements featuring Black SMM exclusively were judged as more stigmatizing than advertisements without couples. Advertisements with diverse (vs. no) couples were considered more eye-catching and motivating. There were minimal effects of couple composition and campaign on PrEP stigma, motivation, and behavior. Focus group participants corroborated concerns about the potential for PrEP advertisements to be stigmatizing, suggesting advertisements featuring Black SMM exclusively could be alienating and fuel conspiracy theories. Focus group participants generally favored diverse and less sexualized advertisements, particularly for public spaces. Findings collectively highlight the potential for targeted PrEP advertisements to stigmatize Black SMM and support diverse representation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Calabrese et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Among transgender women living with HIV (TGWLH) in India, little is understood about the mechanisms through which multiple intersecting stigmas impact HIV care engagement, or intervention strategies that might mitigate this impact. We conducted focus groups with TGWLH (N = 30) in three Indian cities and analysed data using theoretical frameworks related to HIV stigma, gender affirmation, and syndemics. Findings revealed that enacted and anticipated stigma due to transgender identity, HIV, or sex work status, and lack of gender affirmation (e.g., misgendering) in healthcare settings delayed ART initiation and promoted care disengagement. Having supportive physicians and counsellors within ART centres and peer outreach workers facilitated ART initiation, adherence, and retention. Findings also revealed that HIV stigma within TGW communities led to concealment of HIV status or syndemic conditions such as depression and alcohol use, thereby affecting care engagement. However, the TGW community itself was also described as a resilience resource, offering emotional, psychological and tangible support that decreased the impact of discrimination on care engagement. HIV care engagement efforts among Indian TGWLH could be strengthened by reducing intersecting stigmas in healthcare settings and within TGW communities, providing gender-affirming and culturally competent healthcare, addressing psychosocial syndemic conditions, and strengthening support within transgender communities.

Intraoperative computed tomography scanning with O-arm and use of Stealth navigation can improve surgical outcomes in a variety of orthopedic subspecialties. In spine surgery, the accuracy, precision, and safety of pedicle screw and interbody implant placement has improved. This technology is now routinely used in percutaneous pedicle screw placement and minimally invasive sacroiliac joint fusion. Other applications include, but are not limited to, isthmic pars defect repair, lumbosacral pseudoarticulation resection in Bertolotti's syndrome, radiofrequency ablation, and en bloc tumor resection. Intraoperative navigation has numerous applications, and use of this technology should continue to evolve as the technology advances. [ Orthopedics . 2023;46(2):e89-e97.].

Background: Phenylephrine is a selective α 1 -receptor agonist used to manage shock. Current guidelines for septic shock recommend limited utilization of phenylephrine due to the lack of evidence available. This deviates from previous guidelines, which had recommendations of when utilization may be appropriate., Objective: The primary objective of this study was to evaluate mortality in patients receiving phenylephrine for the management of septic shock., Methods: This was a retrospective chart review from September 2015 to September 2017 evaluating all adult patients admitted to an intensive care unit (ICU) on vasopressors for management of septic shock. Patients were divided into 2 groups, those treated with phenylephrine and those treated without phenylephrine. The primary outcome was mortality. Secondary objectives included days on vasopressors and ICU length of stay. Two subgroup analyses were performed: 1 for phenylephrine as first-line therapy and 1 for patients with tachycardia at initiation of vasopressors. Patients started on phenylephrine for salvage therapy were excluded from this study., Results: 499 patients enrolled in the study. 148 (32%) were enrolled in the phenylephrine group. Phenylephrine was associated with an increase in mortality (56% vs 41%; p = 0.003). There was no difference in the days on vasopressors or ICU length of stay. Patients who had ongoing tachycardia were associated with increased mortality with phenylephrine (54% vs 36%, p = 0.02). There was no difference in mortality when phenylephrine was started as the initial vasopressor., Conclusion: Utilization of phenylephrine in septic shock patients, especially those with ongoing tachycardia, was associated with an increased rate of mortality.

Prolyl hydroxylase (PHD) inhibitors are in clinical development for anaemia in chronic kidney disease. Epidemiological studies have reported conflicting results regarding safety of long-term therapeutic haemoglobin (Hgb) rises through PHD inhibition on risk of cardiovascular disease. Genetic variation in genes encoding PHDs can be used as partial proxies to investigate the potential effects of long-term Hgb rises. We used Mendelian randomization to investigate the effect of long-term Hgb level rises through genetically proxied PHD inhibition on coronary artery disease (CAD: 60 801 cases; 123 504 controls), myocardial infarction (MI: 42 561 cases; 123 504 controls) or stroke (40 585 cases; 406 111 controls). To further characterize long-term effects of Hgb level rises, we performed a phenome-wide association study (PheWAS) in up to 451 099 UK Biobank individuals. Genetically proxied therapeutic PHD inhibition, equivalent to a 1.00 g/dl increase in Hgb levels, was not associated (at P < 0.05) with increased odds of CAD; odd ratio (OR) [95% confidence intervals (CI)] = 1.06 (0.84, 1.35), MI [OR (95% CI) = 1.02 (0.79, 1.33)] or stroke [OR (95% CI) = 0.91 (0.66, 1.24)]. PheWAS revealed associations with blood related phenotypes consistent with EGLN's role, relevant kidney- and liver-related biomarkers like estimated glomerular filtration rate and microalbuminuria, and non-alcoholic fatty liver disease (Bonferroni-adjusted P < 5.42E-05) but these were not clinically meaningful. These findings suggest that long-term alterations in Hgb through PHD inhibition are unlikely to substantially increase cardiovascular disease risk; using large disease genome-wide association study data, we could exclude ORs of 1.35 for cardiovascular risk with a 1.00 g/dl increase in Hgb., (© The Author(s) 2022. Published by Oxford University Press.)

Aim: The present study was done to evaluate the knowledge and awareness of different provisional materials, especially polycaprolactone (PCL) and their application in prosthodontic practice., Setting and Design: A questionnaire based survey was carried out to assess the knowledge and awareness of PCL and its applications as provisional material in prosthodontic practice., Materials and Method: A questionnaire-based descriptive study consisting of 10 questions related to different provisional materials and their applications in prosthodontic practice was formulated on Google Forms. The link was created and circulated among the prosthodontist faculty members of various dental institutes and private practitioners of India with the use of digital platforms such as E-mail and social media. The data were collected and examined using Microsoft Excel software for statistical evaluation., Statistical Analysis Used: For this descriptive type of study, knowledge and awareness among prosthodontists across India was evaluated using Microsoft Excel software., Results: The use of PCL was known only to 20.75% of prosthodontists. Moreover, its application and indications are known to only <1% of the study participants. Autopolymerizing resin was most commonly used for the custom tray and temporary base fabrication as well as temporization in crown and bridge prosthesis, while muscle deprogrammer and surgical template were commonly fabricated in heat-cure and clear acrylic resin, respectively. Pattern resin was found to be commonly used in splinting implant impression copings., Conclusion: The use of PCL as a temporary denture base, custom tray, muscle deprogrammer, implant impression splinting, and provisional for crown and bridge and templates should be encouraged and incorporated to get benefits of its characteristic properties. Considering the overall performance of PCL, its use should be incorporated into prosthodontic research and practice., Competing Interests: None

In India and other low-and-middle-income countries, little is known about how intersectional stigma affects MSM engagement in ART. Informed by the Health Stigma and Discrimination Framework, we qualitatively examined how multiple stigmas influence ART engagement among Indian MSM. We conducted 3 focus groups (N = 22) with MSM living with HIV, aged 21-58 years, in Delhi and Hyderabad to identify potential intervention targets and solutions to improve treatment outcomes. Framework analysis and techniques were used to code and analyze translated audio-recordings. Findings revealed enacted stigma, associated with HIV and MSM identity, manifested as familial shame and healthcare discrimination, inhibiting access to support, and decreasing HIV care engagement. Anticipated stigma led to worry about disclosure and societal repercussions. Community-Based-Organizations, ART centers, and family members were primary sources of support, leading to increased ART initiation and retention. Potential solutions included using MSM peer-counselors, increasing social support, and providing HIV education to the general community.

Background: Transgender women (transwomen) are frequently conflated with cisgender sexual minority men (cis-SMM) in HIV research. We examined the impact of socioeconomic and health conditions, and gender-affirming hormones in comparing HIV-related outcomes between cis-SMM and transwomen., Setting: Large tertiary care health system in the Bronx, NY., Methods: Retrospective cohort study of people with HIV receiving care in 2008-2017. We compared retention in care, antiretroviral therapy (ART) prescription, and viral suppression between cis-SMM and transwomen, using modified Poisson regression, adjusting for demographic and clinical factors. Transwomen were further stratified by receipt of estrogen prescription., Results: We included 166 transwomen (1.4%), 1936 cis-SMM (17%), 4715 other cisgender men (41%), and 4745 cisgender women (41%). Transwomen were more likely to have public insurance (78% vs 65%) and mental health (49% vs 39%) or substance use (43% vs 33%) diagnoses than cis-SMM. Compared with cis-SMM, transwomen prescribed estrogen (67% of transwomen) were more likely to be retained [adjusted risk ratio (aRR) 1.15, 95% confidence interval (CI) 1.08 to 1.23), prescribed ART (aRR 1.06, CI 1.01 to 1.11), and virally suppressed (aRR 1.08, CI 1.01 to 1.16). Transwomen not prescribed estrogen were less likely to be retained (aRR 0.92, CI 0.83 to 1.02), prescribed ART (aRR 0.90, CI 0.82 to 0.98), or virally suppressed (aRR 0.85, CI 0.76 to 0.95)., Conclusions: In the context of HIV, socioeconomic factors, comorbidities, and gender-affirming care distinguish transwomen from cis-SMM. Compared with cis-SMM, transwomen who were prescribed estrogen had better HIV care continuum outcomes; transwomen not prescribed estrogen had worse outcomes. These differences should be accounted for in HIV-related research., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Following herniation of the intervertebral disc, there is a need for advanced surgical strategies to protect the diseased tissue from further herniation and to minimize further degeneration. Accordingly, a novel tissue engineered implant for annulus fibrosus (AF) repair was fabricated via three-dimensional fiber deposition and evaluated in a large animal model. Specifically, lumbar spine kinetics were assessed for eight (n = 8) cadaveric ovine lumbar spines in three pure moment loading settings (flexion-extension, lateral bending, and axial rotation) and three clinical conditions (intact, with a defect in the AF, and with the defect treated using the AF repair implant). In ex vivo testing, seven of the fifteen evaluated biomechanical measures were significantly altered by the defect. In each of these cases, the treated spine more closely approximated the intact biomechanics and four of these cases were also significantly different to the defect. The same spinal kinetics were also assessed in a preliminary in vivo study of three (n = 3) ovine lumbar spines 12 weeks post-implantation. Similar to the ex vivo results, functional efficacy of the treatment was demonstrated as compared to the defect model at 12 weeks post-implantation. These promising results motivate a future large animal study cohort which will establish statistical power of these results further elucidate the observed outcomes, and provide a platform for clinical translation of this novel AF repair patch strategy. Ultimately, the developed approach to AF repair holds the potential to maintain the long-term biomechanical function of the spine and prevent symptomatic re-herniation., (Copyright © 2022 Page, Easley, Bonilla, Patel and Puttlitz.)

Objective: There are few prior reports of acute pelvic instrumentation failure in spinal deformity surgery. The objective of this study was to determine if a previously identified mechanism and rate of pelvic fixation failure were present across multiple institutions, and to determine risk factors for these types of failures., Methods: Thirteen academic medical centers performed a retrospective review of 18 months of consecutive adult spinal fusions extending 3 or more levels, which included new pelvic screws at the time of surgery. Acute pelvic fixation failure was defined as occurring within 6 months of the index surgery and requiring surgical revision., Results: Failure occurred in 37 (5%) of 779 cases and consisted of either slippage of the rods or displacement of the set screws from the screw tulip head (17 cases), screw shaft fracture (9 cases), screw loosening (9 cases), and/or resultant kyphotic fracture of the sacrum (6 cases). Revision strategies involved new pelvic fixation and/or multiple rod constructs. Six patients (16%) who underwent revision with fewer than 4 rods to the pelvis sustained a second acute failure, but no secondary failures occurred when at least 4 rods were used. In the univariate analysis, the magnitude of surgical correction was higher in the failure cohort (higher preoperative T1-pelvic angle [T1PA], presence of a 3-column osteotomy; p < 0.05). Uncorrected postoperative deformity increased failure risk (pelvic incidence-lumbar lordosis mismatch > 10°, higher postoperative T1PA; p < 0.05). Use of pelvic screws less than 8.5 mm in diameter also increased the likelihood of failure (p < 0.05). In the multivariate analysis, a larger preoperative global deformity as measured by T1PA was associated with failure, male patients were more likely to experience failure than female patients, and there was a strong association with implant manufacturer (p < 0.05). Anterior column support with an L5-S1 interbody fusion was protective against failure (p < 0.05)., Conclusions: Acute catastrophic failures involved large-magnitude surgical corrections and likely resulted from high mechanical strain on the pelvic instrumentation. Patients with large corrections may benefit from anterior structural support placed at the most caudal motion segment and multiple rods connecting to more than 2 pelvic fixation points. If failure occurs, salvage with a minimum of 4 rods and 4 pelvic fixation points can be successful.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are currently under clinical development for treating anemia in chronic kidney disease (CKD), but it is important to monitor their cardiovascular safety. Genetic variants can be used as predictors to help inform the potential risk of adverse effects associated with drug treatments. We therefore aimed to use human genetics to help assess the risk of adverse cardiovascular events associated with therapeutically altered EPO levels to help inform clinical trials studying the safety of HIF-PHIs. By performing a genome-wide association meta-analysis of EPO (n = 6,127), we identified a cis-EPO variant (rs1617640) lying in the EPO promoter region. We validated this variant as most likely causal in controlling EPO levels by using genetic and functional approaches, including single-base gene editing. Using this variant as a partial predictor for therapeutic modulation of EPO and large genome-wide association data in Mendelian randomization tests, we found no evidence (at p < 0.05) that genetically predicted long-term rises in endogenous EPO, equivalent to a 2.2-unit increase, increased risk of coronary artery disease (CAD, OR [95% CI] = 1.01 [0.93, 1.07]), myocardial infarction (MI, OR [95% CI] = 0.99 [0.87, 1.15]), or stroke (OR [95% CI] = 0.97 [0.87, 1.07]). We could exclude increased odds of 1.15 for cardiovascular disease for a 2.2-unit EPO increase. A combination of genetic and functional studies provides a powerful approach to investigate the potential therapeutic profile of EPO-increasing therapies for treating anemia in CKD., Competing Interests: Declaration of interests C.E.H. was awarded an MRC iCASE studentship (MR/P016065/1), which was cofunded by GSK and the MRC for the duration of the study. GSK are undertaking clinical development into a novel PHI and have given permission to publish this work alongside an internal review of the manuscript. A.Y.C. is an employee of GSK, is a shareholder of GSK stock, and was involved in the study design, interpretation of the data, and writing of the paper. V.V.P. was an employee of GSK at the time of the study conception and design. He was involved in interpreting the data and writing of the paper and is a shareholder of GSK and Roche Holding AG stocks. D.M.W. was an employee of GSK at the time of the study conception and design and was involved in the interpretation of the data and writing of the paper. H.L.L. and M.A.N. received support from a consulting contract between Data Tecnica International and the National Institute on Aging (NIA), National Institutes of Health (NIH). They were involved in data analysis and review of the manuscript. N.V. is a full-time employee of Regeneron Pharmaceutical Inc. and receives stock options and restricted stock units as compensation. D.D.J. received support from the Center of Human Health and the Environment P30ESO25128 grant. F.I. is an AbbVie employee and receives stocks from AbbVie, which has not been involved in this work at any level., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Study Design: Rat spine fusion model., Objective: The present study aimed to determine whether administration of osteoprotegerin (OPG) in a rat model of spinal fusion increases bone volume, bone density, and decreases osteoclasts in the fusion mass., Summary of Background Data: OPG is a soluble RANK-ligand inhibitor that blocks osteoclast differentiation and activation. This makes it a potential agent to control the remodeling process and enhance bone mass during spinal fusion., Materials and Methods: Forty-eight male Sprague-Dawley rats received a one-level spinal fusion of L4-L5 with bone allograft. Rats were then divided into four groups according to initiation of treatment: (1) saline on day 0 (saline), (2) OPG on day 0 (OPG D0), (3) OPG on day 10 (OPG D10), and (4) OPG on day 21 (OPG D21) postsurgery. After their initial injection, rats received weekly subcutaneous injections of OPG (10 mg/kg) and were euthanized six weeks postsurgery. MicroCT analysis of the fusion site and histological analysis of bone surface for quantification of osteoclast lining was performed., Results: Increased bone volume in the fusion site and around the spinous process was seen in OPG D0 and OPG D10 when compared with saline. Mean trabecular thickness was greater in all groups receiving OPG compared with saline, with OPG D0 and OPG D10 having significantly greater mean trabecular thickness than OPG D21. All OPG groups had less bone surface lined with osteoclasts when compared with Saline, with OPG D0 and OPG D10 having fewer than OPG D21., Conclusions: This study indicates that OPG inhibited osteoclast bone resorption, which led to greater bone at the fusion site. Future studies investigating OPG on its own or in combination with an osteogenic factor to improve spinal fusion outcomes are warranted to further elucidate its potential therapeutic effect., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Case: Ten days after L3-L5 instrumented posterior lumbar spinal fusion, an 85-year-old woman developed Grade 4 spondylolisthesis at L5-S1 after a minor fall. She underwent posterior open reduction and internal fixation with extension of fusion from L2 to the pelvis. The preexisting hardware at L5 caused partial laceration of the right L5 nerve root. One year after surgery, computed tomography demonstrated maintenance of correction and fusion at L5-S1., Conclusion: High-grade lumbosacral spondylolisthesis can occur with minor trauma after short-segment lumbar fusion. Maintenance of correction and fusion is achievable with posterior open reduction and internal fixation to the pelvis alone. Preexisting hardware can damage nerve roots causing permanent neurological deficits., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B896)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)