VALOR-CKD: A Multicenter, Randomized, Double-Blind Placebo-Controlled Trial Evaluating Veverimer in Slowing Progression of CKD in Patients with Metabolic Acidosis.

Significance Statement: Metabolic acidosis is a common complication of CKD and is associated with more rapid decline of kidney function, but well-powered controlled randomized trials testing the effect of treating metabolic acidosis on slowing CKD progression have not been conducted. The VALOR-CKD study randomized 1480 individuals with CKD and metabolic acidosis, across 320 sites to placebo or veverimer (a novel hydrochloric acid binder). The findings did not demonstrate the efficacy of veverimer in slowing CKD progression, but the difference in serum bicarbonate between placebo and drug arms was only approximately 1 mEq/L.

Manipulation Under Anesthesia and/or Lysis of Adhesions After Anterior Cruciate Ligament Reconstruction in Female Basketball Players: Does Race Play a Role?

Background: Arthrofibrosis can limit function and return to sport after anterior cruciate ligament (ACL) reconstruction. Previously reported risk factors for developing arthrofibrosis after ACL reconstruction include female sex, age <18 years, time from injury to surgery <28 days, concomitant meniscal repair, prolonged immobilization, and genetic factors. There is a lack of evidence regarding whether race plays a significant role.

Increased human complement pathway regulatory protein gene dose is associated with increased endothelial expression and prolonged survival during ex-vivo perfusion of GTKO pig lungs with human blood.

Introduction: Expression of human complement pathway regulatory proteins (hCPRP's) such as CD46 or CD55 has been associated with improved survival of pig organ xenografts in multiple different models. Here we evaluate the hypothesis that an increased human CD46 gene dose, through homozygosity or additional expression of a second hCPRP, is associated with increased protein expression and with improved protection from injury when GTKO lung xenografts are perfused with human blood.

Methods: Twenty three GTKO lungs heterozygous for human CD46 (GTKO.

Augmentation of Massive Rotator Cuff Repairs Using Biceps Transposition Without Tenotomy Improves Clinical and Patient-Reported Outcomes: The Biological Superior Capsular Reconstruction Technique.

Purpose: To evaluate the outcomes of a consecutive series of patients after transposition of the biceps without tenotomy (biological superior capsular reconstruction [bio-SCR] technique) to augment massive rotator cuff repairs.

Methods: Thirty massive rotator cuff tears repaired and augmented using the bio-SCR technique between June 2018 and July 2021 were identified and retrospectively reviewed. American Shoulder and Elbow Surgeons (ASES) scores, visual analog scale pain scores, supraspinatus and infraspinatus strength, and range of motion were collected preoperatively and postoperatively.

Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breast milk feeding.

Background: Although there have been many studies on antibody responses to SARS-CoV-2 in breast milk, very few have looked at the fate of these in the infant, and whether they are delivered to immunologically relevant sites in infants.

Methods: Mother/infant pairs (mothers who breast milk fed and who were SARS-CoV-2 vaccinated before or after delivery) were recruited for this cross-sectional study. Mother blood, mother breast milk, infant blood, infant nasal specimen, and infant stool was tested for IgA and IgG antibodies against SARS-CoV-2 spike trimer.

Image-Free Robotic-Assisted Total Knee Arthroplasty Results in Quicker Recovery but Equivalent One-Year Outcomes Compared to Conventional Total Knee Arthroplasty.

Background: Few studies have addressed whether robotic-assisted total knee arthroplasty (RA-TKA) significantly impacts functional outcomes. This study was conducted to determine whether image-free RA-TKA improves function compared to conventional total knee arthroplasty (C-TKA), performed without the utilization of robotics or navigation, using the Minimal Clinically Important Difference (MCID) and Patient Acceptable Symptom State (PASS) as measures of meaningful clinical improvement.

Methods: A multicenter propensity score-matched retrospective study was conducted of RA-TKA using an image-free robotic system and C-TKA cases at an average follow-up of 14 months (range, 12 months to 20 months).

Design and population of the VALOR-CKD study: a multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of veverimer in slowing progression of chronic kidney disease in patients with metabolic acidosis.

Background: Whether treating metabolic acidosis slows progression of chronic kidney disease (CKD) has not been established. Veverimer is a novel hydrochloric acid binder that removes acid from the gastrointestinal tract leading to an increase in serum bicarbonate; it is being developed to treat metabolic acidosis with the goal of slowing progression of CKD.

Methods: The VALOR-CKD trial is an international, randomized, multicenter, double-blind, placebo-controlled study designed to evaluate the effect of once-daily veverimer on kidney disease progression in patients with metabolic acidosis and CKD.

The successful migration of total joint arthroplasty from the hospital inpatient to outpatient ASC setting.

Background: This study was undertaken to analyze the clinical results and complication rate of patients undergoing outpatient total joint arthroplasty by a single orthopedic group. All surgeries were performed in the practice-owned ambulatory surgery center (ASC).

Methods: All patients indicated for outpatient total joint arthroplasty from 2016-2019 with complete pre and post-operative patient reported outcomes were enrolled in the study including hip, knee and partial knee replacements.

Pig-to-baboon lung xenotransplantation: Extended survival with targeted genetic modifications and pharmacologic treatments.

Galactosyl transferase knock-out pig lungs fail rapidly in baboons. Based on previously identified lung xenograft injury mechanisms, additional expression of human complement and coagulation pathway regulatory proteins, anti-inflammatory enzymes and self-recognition receptors, and knock-down of the β4Gal xenoantigen were tested in various combinations. Transient life-supporting GalTKO.

Unicompartmental Knee Arthroplasty Is Not Associated With Increased Revision Rates in Obese Patients.

Background: There is controversy among arthroplasty surgeons in regard to performing unicompartmental knee arthroplasty (UKA) in obese patients based on current literature. The aim of this study is to investigate whether UKA is associated with increased complications and revision rates in obese (body mass index [BMI] > 30 kg/m), morbidly obese (BMI > 40 kg/m), and super morbid obese (BMI > 50 kg/m) patients.

Methods: We retrospectively reviewed all UKAs performed at our institution from January 2008 to December 2017.

Assessment of the Potential for Veverimer Drug-Drug Interactions.

Veverimer is a polymer being developed as a potential treatment of metabolic acidosis in patients with chronic kidney disease. Veverimer selectively binds and removes hydrochloric acid from the gastrointestinal tract, resulting in an increase in serum bicarbonate. Veverimer is not systemically absorbed, so potential drug-drug interactions (DDIs) are limited to effects on the absorption of other oral drugs through binding to veverimer in the gastrointestinal tract or increases in gastric pH caused by veverimer binding to hydrochloric acid.

Predictors of acromial and scapular stress fracture after reverse shoulder arthroplasty: a study by the ASES Complications of RSA Multicenter Research Group.

Background: Acromial (ASF) and scapular spine (SSF) stress fractures are well-recognized complications of reverse shoulder arthroplasty (RSA), but much of the current data are derived from single-center or single-implant studies with limited generalizability. This study from the American Shoulder and Elbow Surgeons (ASES) Complications of Reverse Shoulder Arthroplasty Multicenter Research Group determined the incidence of ASF/SSF after RSA and identified preoperative patient characteristics associated with their occurrence.

Method: Fifteen institutions including 21 ASES members across the United States participated in this study.

Partial Rotator Cuff Repair for Massive Tears Rarely Require Revision Surgery.

Purpose: To determine the significance of initial and residual rotator cuff tear defect size on the need for revision surgery or additional nonsurgical therapy, in a consecutive group of patients undergoing partial repair of massive rotator cuff tears.

Methods: A retrospective chart review was carried out for all arthroscopic rotator cuff repairs performed by a single surgeon between January of 2013 and December of 2016. All patients with massive rotator cuff tears (>30 cm) who underwent partial repair were included in the study.

Exosomes isolated from human cardiosphere-derived cells attenuate pressure overload-induced right ventricular dysfunction.

Objectives: Cardiosphere-derived cell (CDC) transplantation has been shown to attenuate right ventricular (RV) dysfunction in patients with hypoplastic left heart syndrome. However, live cell transplantation requires complex handling protocols that may limit its use. Exosomes are protein and nucleic acid-containing nanovesicles secreted by many cell types, including stem cells, which have been shown to exert a cardioprotective effect comparable with whole cells following myocardial injury.

Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: a multicentre, randomised, blinded, placebo-controlled, 40-week extension.

Background: Metabolic acidosis, a complication of chronic kidney disease, causes protein catabolism and bone demineralisation and is associated with adverse kidney outcomes and mortality. Veverimer, a non-absorbed, counterion-free, polymeric drug candidate selectively binds and removes hydrochloric acid from the gastrointestinal lumen.

Methods: We did a multicentre, randomised, blinded, placebo-controlled, 40-week extension of a 12-week parent study at 29 sites (hospitals and specialty clinics) in seven countries (Bulgaria, Georgia, Hungary, Serbia, Slovenia, Ukraine, and the USA).

Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: a multicentre, randomised, double-blind, controlled, phase 3 trial.

Background: Patients with advanced chronic kidney disease lose the capacity to fully excrete endogenous acid, resulting in chronic metabolic acidosis that increases the risk of disease progression and causes muscle catabolism and bone resorption. Veverimer, a non-absorbed, counterion-free, polymeric drug, selectively binds and removes hydrochloric acid from the gastrointestinal lumen, unlike current oral sodium bicarbonate therapy for metabolic acidosis that only neutralises accumulated acid. We assessed the efficacy and safety of veverimer as a treatment for metabolic acidosis in patients with chronic kidney disease.

Thromboxane and histamine mediate PVR elevation during xenogeneic pig lung perfusion with human blood.

Background: Elevated pulmonary vascular resistance (PVR), platelet adhesion, coagulation activation, and inflammation are prominent features of xenolung rejection. Here, we evaluate the role of thromboxane and histamine on PVR, and their contribution to other lung xenograft injury mechanisms.

Methods: GalTKO.

Feasibility of basic transesophageal echocardiography in hemorrhagic shock: potential applications during resuscitative endovascular balloon occlusion of the aorta (REBOA).

Background: There are numerous studies in the cardiovascular literature that have employed transesophageal echocardiography (TEE) in swine models, but data regarding the use of basic TEE in swine models is limited. The primary aim of this study is to describe an echocardiographic method that can be used with relative ease to qualitatively assess cardiovascular function in a porcine hemorrhagic shock model using resuscitative endovascular balloon occlusion of the aorta (REBOA).

Methods: Multiplane basic TEE exams were performed in 15 during an experimental hemorrhage model using REBOA.

Vascularized Thymosternal Composite Tissue Allo- and Xenotransplantation in Nonhuman Primates: Initial Experience.

Background: Vascularized composite allotransplantation is constrained by complications associated with standard immunosuppressive strategies. Vascularized thymus and bone marrow have been shown to promote prolonged graft survival in composite organ and soft-tissue vascularized composite allotransplantation models. We report development of a nonhuman primate vascularized thymosternal composite tissue transplant model as a platform to address donor-specific immune tolerance induction strategies.

Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD.

Background And Objectives: Metabolic acidosis is common in patients with CKD and has significant adverse effects on kidney, muscle, and bone. We tested the efficacy and safety of TRC101, a novel, sodium-free, nonabsorbed hydrochloric acid binder, to increase serum bicarbonate in patients with CKD and metabolic acidosis.

Design, Setting, Participants, & Measurements: One hundred thirty-five patients were enrolled in this randomized, double-blind, placebo-controlled, multicenter, in-unit study (designated the TRCA-101 Study).