Distinct Mitochondrial Pathologies Caused by Mutations of the Proximal Tubular Enzymes EHHADH and GATM

The mitochondria of the proximal tubule are essential for providing energy in this nephron segment, whose ATP generation is almost exclusively oxygen dependent. In addition, mitochondria are involved in a variety of metabolic processes and complex signaling networks. Proximal tubular mitochondrial dysfunction can therefore affect renal function in very different ways. Two autosomal dominantly inherited forms of renal Fanconi syndrome illustrate how multifaceted mitochondrial pathology can be: Mutation of EHHADH, an enzyme in fatty acid metabolism, results in decreased ATP synthesis and a consecutive transport defect. In contrast, mutations of GATM, an enzyme in the creatine biosynthetic pathway, leave ATP synthesis unaffected but do lead to mitochondrial protein aggregates, inflammasome activation, and renal fibrosis with progressive renal failure. In this review article, the distinct pathophysiological mechanisms of these two diseases are presented, which are examples of the spectrum of proximal tubular mitochondrial diseases

EAST/SeSAME Syndrome and Beyond: The Spectrum of Kir4.1- and Kir5.1-Associated Channelopathies

In 2009, two groups independently linked human mutations in the inwardly rectifying K+ channel Kir4.1 (gene name KCNJ10) to a syndrome affecting the central nervous system (CNS), hearing, and renal tubular salt reabsorption. The autosomal recessive syndrome has been named EAST (epilepsy, ataxia, sensorineural deafness, and renal tubulopathy) or SeSAME syndrome (seizures, sensorineural deafness, ataxia, intellectual disability, and electrolyte imbalance), accordingly. Renal dysfunction in EAST/SeSAME patients results in loss of Na+, K+, and Mg2+ with urine, activation of the renin–angiotensin–aldosterone system, and hypokalemic metabolic alkalosis. Kir4.1 is highly expressed in affected organs: the CNS, inner ear, and kidney. In the kidney, it mostly forms heteromeric channels with Kir5.1 (KCNJ16). Biallelic loss-of-function mutations of Kir5.1 can also have disease significance, but the clinical symptoms differ substantially from those of EAST/SeSAME syndrome: although sensorineural hearing loss and hypokalemia are replicated, there is no alkalosis, but rather acidosis of variable severity; in contrast to EAST/SeSAME syndrome, the CNS is unaffected. This review provides a framework for understanding some of these differences and will guide the reader through the growing literature on Kir4.1 and Kir5.1, discussing the complex disease mechanisms and the variable expression of disease symptoms from a molecular and systems physiology perspective. Knowledge of the pathophysiology of these diseases and their multifaceted clinical spectrum is an important prerequisite for making the correct diagnosis and forms the basis for personalized therapies

Do Medial Pivot Kinematics Correlate With Patient-Reported Outcomes After Total Knee Arthroplasty?

Background Many total knee arthroplasty (TKA) implants are designed to facilitate a medial pivot kinematic pattern. The purpose of this study was to determine whether intraoperative medial pivot kinematic patterns are associated with improved patient outcomes. Methods A retrospective review of consecutive primary TKAs was performed. Sensor-embedded tibial trials determined kinematic patterns intraoperatively. The center of rotation (COR) was identified from 0° to 90° and from 0° to terminal flexion, and designated medial-pivot or non-medial pivot based on accepted criteria. Patient-reported outcomes were measured preoperatively and at minimum one-year follow-up. Results The analysis cohort consisted of 141 TKAs. Mean age and median BMI were 63.7 years and 33.8 kg/m2, respectively. Forty-percent of TKAs demonstrated a medial pivot kinematic pattern intraoperatively. A medial pivot pattern was more common with posterior cruciate-retaining (CR) and posterior cruciate-substituting/anterior lipped (CS) implants when compared to posterior stabilized (PS) TKAs (P ≤.0150). Regardless of bearing type, minimum one-year Knee Society scores and UCLA activity level did not significantly differ based on medial vs non-medial pivot patterns (P ≥.292). For patients with posterior cruciate-sacrificing implants, there were trends for greater median improvement in Knee Society objective (46 vs 31.5 points, P =.057) and satisfaction (23 vs 14 points, P =.067) scores in medial pivot knees. Conclusion A medial pivot pattern may not significantly govern clinical success after TKA based on intraoperative kinematics and modern outcome measures. Further research is warranted to determine if a particular kinematic pattern promotes optimal clinical outcomes

Do Antibiotic Intramedullary Dowels Assist in Eradicating Infection in Two-Stage Resection for Septic Total Knee Arthroplasty?

Background Evidence suggests approximately 40% of intramedullary (IM) canals are culture positive at resection for infected knee arthroplasty. While commonly utilized, no clinical data on the efficacy of antibiotic-eluding IM dowels exist. We quantified treatment success with and without the use of antibiotic-eluding IM dowels in two-stage treatment of periprosthetic knee infection using static and articulating antibiotic cement spacers. Methods 109 consecutive patients who underwent two-stage treatment for periprosthetic knee infection were reviewed. Treatment failure, defined as repeat resection before reimplantation or recurrent infection within 6 months of reimplantation, was evaluated based on spacer type and use of IM dowels, accounting for infection type and systemic host and local extremity grade. Results After exclusions for confounds, articulating spacers without IM dowels were used in 49 (57.7%) cases, articulating spacers with IM dowels in 14 cases (16.5%), and static spacers with IM dowels in 22 (25.9%) cases. Treatment success regardless of infection classification was 85.7% for articulating spacers with IM dowels, 89.8% for articulating spacers without IM dowels, and 68.2% for static spacers with IM dowels (P = .074). In chronically infected poor hosts with compromised extremities, treatment success remained highest in patients with articulating spacers with (90.9%) or without (92.9%) IM dowels compared with static spacers with IM dowels (68.4%) (P = .061). Conclusion Findings suggest that the use of IM dowels did not enhance infection eradication above and beyond that observed for articulating spacers alone, including in the worst cases involving chronically infected poor hosts with compromised extremities

How Has COVID-19 Affected Our Orthopedic Implant Industry Partners? Implications for the Surgeon-Industry Relationship in 2020 and Beyond

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background The COVID-19 pandemic has had far-reaching societal and financial consequences. The purpose of this study was to evaluate how COVID-19 has affected AAHKS industry partners and the surgeon-industry relationship, emphasizing education, resource allocation, and strategic direction for the 2nd half of 2020. Methods AAHKS industry partners were contacted to participate in a blinded survey and optional interview with the AAHKS Industry Relations Committee. Based on the results, a group of AAHKS member surgeons with disparate practice types were asked to postulate on how the COVID-19 pandemic has and will affect their practice and relationship with Industry. Results AAHKS industry partner responses indicated decreased resource allocation for regional, “other national,” and AAHKS annual meetings (67%, 55%, and 30%, respectively). Web-based educational content was expected to increase in 2020 and will likely remain a point of emphasis in 2021 (100% and 70% of responders). For Q3/Q4 2020, a significant emphasis was placed on site of service/outpatient TJA and COVID-19-related safety measures (70% and 90% of responders), as well as increased availability of instrumentation and implants (40% and 60%, respectively). Conclusion The COVID-19 pandemic has altered the orthopedic landscape for the foreseeable future. Survey responses by AAHKS industry partners demonstrate a continued commitment to surgeon education with and increasing shift to a web-based platform. Increased resource allocation for outpatient TJA and COVID-19-related safety measures were significant. Articulating optimal mechanisms to aid industry in supporting surgeons with different practice models to meet demand during the second half of fiscal year 2020 will be critical

Variability Between Full-Length Lateral Radiographs and Standard Short Knee Radiographs When Evaluating Posterior Tibial Slope in Revision ACL Patients

BACKGROUND: Increased posterior tibial slope (PTS) has been identified as a risk factor for failure after anterior cruciate ligament (ACL) reconstruction. Correction of PTS may improve outcomes after revision ACL reconstruction. There are conflicting reports demonstrating the measurement of the PTS on standard short knee (SSK) radiographs versus full-length lateral (FLL) radiographs including the entire tibia. PURPOSE/HYPOTHESIS: To compare PTS measurements between SSK and FLL radiographs in patients who failed primary ACL reconstruction. It was hypothesized that there would be high variability between the SSK and FLL radiographic measurements. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: The medial and lateral PTS were measured on the SSK and FLL radiographs of 33 patients with failed primary ACL reconstructions. All measurements were performed by 2 trained independent observers (A.A.M., J.S.), and inter- and intraobserver reliability were calculated using the intraclass correlation coefficient (ICC). Measurements recorded by the observer with the higher intraobserver ICC were used for comparison of the PTS on SSK versus FLL radiographs. RESULTS: Both the inter- and the intraobserver reliability values of the PTS measurements were excellent. There was a significant difference in mean PTS on the medial plateau as measured on the SSK and FLL radiographs (11.2°± 5.3° vs 12.5°± 4.6°; CONCLUSION: Results indicated that FLL and SSK radiographs are not interchangeable measurements for PTS associated with failed ACL reconstruction. Because FLL radiographs demonstrate less variability than SSK radiographs, we recommend obtaining them to evaluate these complex patients

Variability Between Full-Length Lateral Radiographs and Standard Short Knee Radiographs When Evaluating Posterior Tibial Slope in Revision ACL Patients.

BACKGROUND: Increased posterior tibial slope (PTS) has been identified as a risk factor for failure after anterior cruciate ligament (ACL) reconstruction. Correction of PTS may improve outcomes after revision ACL reconstruction. There are conflicting reports demonstrating the measurement of the PTS on standard short knee (SSK) radiographs versus full-length lateral (FLL) radiographs including the entire tibia. PURPOSE/HYPOTHESIS: To compare PTS measurements between SSK and FLL radiographs in patients who failed primary ACL reconstruction. It was hypothesized that there would be high variability between the SSK and FLL radiographic measurements. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: The medial and lateral PTS were measured on the SSK and FLL radiographs of 33 patients with failed primary ACL reconstructions. All measurements were performed by 2 trained independent observers (A.A.M., J.S.), and inter- and intraobserver reliability were calculated using the intraclass correlation coefficient (ICC). Measurements recorded by the observer with the higher intraobserver ICC were used for comparison of the PTS on SSK versus FLL radiographs. RESULTS: Both the inter- and the intraobserver reliability values of the PTS measurements were excellent. There was a significant difference in mean PTS on the medial plateau as measured on the SSK and FLL radiographs (11.2°± 5.3° vs 12.5°± 4.6°; CONCLUSION: Results indicated that FLL and SSK radiographs are not interchangeable measurements for PTS associated with failed ACL reconstruction. Because FLL radiographs demonstrate less variability than SSK radiographs, we recommend obtaining them to evaluate these complex patients

Experimental and modeling study of the autoignition of 1-hexene/iso-octane mixtures at low temperatures

Autoignition delay times have been measured in a rapid compression machine at Lille at temperatures after compression from 630 to 840 K, pressures from 8 to 14 bar, \Phi = 1 and for a iso octane/1 hexene mixture containing 82% iso-octane and 18% 1 hexene. Results have shown that this mixture is strongly more reactive than pure iso-octane, but less reactive than pure 1 hexene. It exhibits a classical low temperature behaviour, with the appearance of cool flame and a negative temperature coefficient region. The composition of the reactive mixture obtained after the cool flame has also been determined. A detailed kinetic model has been obtained by using the system EXGAS, developed in Nancy for the automatic generation of kinetic mechanisms, and an acceptable agreement with the experimental results has been obtained both for autoignition delay times and for the distribution of products. A flow rate analysis reveals that the crossed reactions between species coming from both reactants (like H-abstractions or combinations) are negligible in the main flow consumption of the studied hydrocarbons. The ways of formation of the main primary products observed and the most sensitive rate constants have been identified

Internet Promotion of Direct Anterior Approach Total Hip Arthroplasty by Members of the American Association of Hip and Knee Surgeons

Introduction The Direct Anterior approach (DAA) in total hip arthroplasty (THA) is of significant interest to both patients and surgeons, largely due to intense marketing. This study addressed the question, ‘What is the level of promotion of DAA THA on the internet by American Association of Hip and Knee Surgeons (AAHKS) members?’ Methods An internet search was performed to identify surgeon-specific websites for each member of the AAHKS using the members’ full name and a previously published set of criteria. Each website was evaluated utilizing a questionnaire to systematically identify claims made regarding proposed DAA specific risks, benefits, as well as the presence/absence of supporting data. Results We identified 1,855 qualified websites. The DAA was referenced on 22.8% (423/1,855) of these websites. Claims regarding DAA specific benefits included; less invasive/muscle sparing (46.3%), quicker recovery (45.2%), decreased pain (28.1%), decreased hospital stay (22.0%), and decreased dislocation risk (16.3%). Potential DAA risks including lateral femoral cutaneous nerve injury, peri-prosthetic/greater trochanteric fracture, and wound complication/hematoma were addressed on only 4.7%, 3.1%, and 1.7% of websites, respectively. Supporting peer-reviewed literature was identified on only 3.6% of DAA websites. Conclusions Over one fifth of AAHKS members promoted the DAA on the internet. Member websites claimed DAA benefits such as faster recovery and decreased pain approximately nine times more frequently than any potential risk of the procedure (p < 0.001). While AAHKS policy does not regulate member marketing, it is the responsibility of all orthopaedic surgeons to disseminate accurate, validated information concerning the procedures we perform