Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin

Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity and facilitates their rapid clearance from circulation after hemolysis. Humans possess three main phenotypes of Hp, designated Hp 1-1, Hp 2-1, and Hp 2-2. These variants exhibit diverse structural configurations and have been reported to be functionally nonequivalent. We have investigated the functional and redox properties of Hb–Hp complexes prepared using commercially fractionated Hp and found that all forms exhibit similar behavior. The rate of Hb dimer binding to Hp occurs with bimolecular rate constants of ~0.9 μM−1 s−1, irrespective of the type of Hp assayed. Although Hp binding does accelerate the observed rate of HbO2 autoxidation by dissociating Hb tetramers into dimers, the rate observed for these bound dimers is three- to fourfold slower than that of Hb dimers free in solution. Co-incubation of ferric Hb with any form of Hp inhibits heme loss to below detectable levels. Intrinsic redox potentials (E1/2) of the ferric/ferrous pair of each Hb–Hp complex are similar, varying from +54 to +59 mV (vs NHE), and are essentially the same as reported by us previously for Hb–Hp complexes prepared from unfractionated Hp. All Hb–Hp complexes generate similar high amounts of ferryl Hb after exposure to hydrogen peroxide. Electron paramagnetic resonance data indicate that the yields of protein-based radicals during this process are approximately 4 to 5% and are unaffected by the variant of Hp assayed. These data indicate that the Hp fractions examined are equivalent to one another with respect to Hb binding and associated stability and redox properties and that this result should be taken into account in the design of phenotype-specific Hp therapeutics aimed at countering Hb-mediated vascular disease

Increased prevalence of lower extremity soft tissue injuries and surgeries in patients with anorexia nervosa and bulimia nervosa

PURPOSE: An abundance of literature exists linking eating disorders and fracture risk. However, no studies, to our knowledge, have investigated the impact of eating disorders on lower extremity soft tissue injury or surgery risk. The purpose of this study was to determine if anorexia nervosa and bulimia nervosa are associated with prevalence of lower extremity soft tissue injuries and surgeries. METHODS: Patients with anorexia nervosa or bulimia nervosa over 2010-2020 were identified through the International Classification of Diseases (ICD) codes in the PearlDiver Claims Database. Patients were matched by age, gender, comorbidities, record dates, and region to control groups without anorexia or bulimia. Soft tissue injuries were identified through ICD codes, and surgeries were identified through Current Procedural Terminology codes. Differences in relative prevalence were analyzed using chi-square analysis. RESULTS: Patients with anorexia had a significantly increased prevalence of meniscus tears (RR = 1.57, CI 1.22-2.03,  = 0.001) or deltoid ligament sprains (RR = 1.83, CI 1.10-3.03,  = 0.025), and patients with bulimia had a significantly increased prevalence of meniscus tears (RR = 1.98, CI 1.56-2.51,  \u3c 0.001), medial collateral ligament sprains (RR = 3.07, CI 1.72-5.48,  \u3c 0.001), any cruciate ligament tears (RR = 2.14, CI 1.29-3.53,  = 0.004), unspecified ankle sprains (RR = 1.56, CI 1.22-1.99,  \u3c 0.001), or any ankle ligament sprains (RR = 1.27, CI 1.07-1.52,  = 0.008). Patients with anorexia had a significantly increased prevalence of anterior cruciate ligament reconstructions (RR = 2.83, CI 1.12-7.17,  = 0.037) or any meniscus surgeries (RR = 1.54, CI 1.03-2.29,  = 0.042), and patients with bulimia had a significantly increased prevalence of partial meniscectomies (RR = 1.80, CI 1.26-2.58,  = 0.002) or any meniscus surgeries (RR = 1.83, CI 1.29-2.60,  \u3c 0.001). CONCLUSIONS: Anorexia and bulimia are associated with increased prevalence of soft tissue injuries and surgeries. Orthopedic surgeons should be aware of this risk, and patients presenting to clinics should be informed of the risks associated with these diagnoses and provided with resources promoting recovery to help prevent further injury or surgery

SLAP repair and bicep tenodesis: a comparison of utilization and revision rates for SLAP tears

HYPOTHESIS: The management of superior labrum anterior to posterior (SLAP) tears typically consists of either repair or biceps tenodesis (BT). While repair is more frequently recommended in younger patients, patients older than 40 years are often treated with BT. The purpose of this study is to determine whether there has been a change in utilization of these procedures over the past decade with respect to patient age as well as compare reoperation rates between the two procedures. METHODS: The Pearldiver database was queried to identify BT and SLAP repairs indicated for SLAP tears performed from 2010 to 2019. The primary outcome was utilization rate, stratified by age. A secondary outcome was 2-year shoulder reoperation rates. Trends were reported in terms of compounded annual growth rate. Outcome analysis was conducted using univariate and multivariable analysis. RESULTS: From 2010 to 2019, SLAP repair was the most common procedure performed for SLAP tears. Regardless of age, BT performed for SLAP tear had a significantly increased utilization rate; whereas, SLAP repair had a significantly decreased utilization rate. SLAP repair was more commonly performed in younger patients compared to BT. Following multivariable analysis, patients who underwent SLAP repair had significantly higher odds (odds ratio (OR): 1.453; 95% confidence interval (CI): 1.26-1.68; \u3c .001) of requiring an arthroscopic reoperation within 2 years when compared to those who underwent BT with no significant difference with respect to 2-year open reoperation. CONCLUSION: Although SLAP repair is still more commonly used to treat SLAP tears than BT, especially for younger patients, the utilization of SLAP repair is decreasing while BT is increasing. The increased utilization of BT may be associated with lower rates of shoulder reoperation for problematic SLAP tears

Total Shoulder Arthroplasty: Antibiotic Allergies Increase Risk of Postoperative Complications

BACKGROUND: Periprosthetic infections after total shoulder arthroplasty (TSA) are associated with devastating complications and prolonged treatment. Patients with identified antibiotic allergy (ABX) may be at increased risk for complications because of suboptimal preincisional prophylaxis. This study aims to quantify the risk of postoperative outcomes and complications for patients undergoing TSA with a history of ABX. METHODS: Retrospective cohort analysis of patient data was conducted using the PearlDiver Patient Records Database. Patients who underwent TSA for osteoarthritis were identified using Current Procedural Terminology and International Classification of Diseases codes and were stratified based on self-reported (1) penicillin, (2) sulfonamide, or (3) other antibiotic allergies. We analyzed patient demographics, comorbidities, 90-day medical complications, and rate of revision at 30 days, 90 days, 1 year, and 2 years. RESULTS: In total, 85,606 patients who underwent TSA for osteoarthritis from 2010 to 2018 were identified, of whom 7,836 (9.15%) had a reported ABX. Univariate analysis found the ABX cohort was younger (67.5 versus 67.7 year; P = 0.042), more often female (67.57% versus 54.79%; P \u3c 0.001), and more likely to have Elixhauser comorbidities than nonallergic control subjects. Multivariate analysis found patients who reported ABX had increased likelihood of periprosthetic joint infection (PJI) within 30 days (odds ratio [OR]: 3.129), 1 year (OR: 2.016), and 2 years of surgery (OR: 2.221). Patients with reported ABX had increased likelihood of postoperative anemia (OR: 1.126), blood transfusion (OR: 1.238), and readmission (OR: 1.585) within 90 days of surgery. Patients with penicillin allergy had a greater incidence of revision due to PJI at 30 days (OR: 4.811), 90 days (OR: 2.91), 1 year (OR: 2.105), and 2 years (OR: 2.72). Rates of reported ABX increased from 2010 to 2018 (8.60% to 10.91%; P = 0.001) in patients undergoing TSA. CONCLUSION: Patients undergoing TSA with a history of ABX had a higher risk of readmission, postoperative anemia, blood transfusions, and PJI. These findings support critical assessment and clarification of reported allergies before TSA and possibly the use of preoperative allergy testing. LEVEL OF EVIDENCE: Level 3 therapeutic study

Increased prevalence of lower extremity soft tissue injuries and surgeries in patients with anorexia nervosa and bulimia nervosa

An abundance of literature exists linking eating disorders and fracture risk. However, no studies, to our knowledge, have investigated the impact of eating disorders on lower extremity soft tissue injury or surgery risk. The purpose of this study was to determine if anorexia nervosa and bulimia nervosa are associated with prevalence of lower extremity soft tissue injuries and surgeries. Patients with anorexia nervosa or bulimia nervosa over 2010–2020 were identified through the International Classification of Diseases (ICD) codes in the PearlDiver Claims Database. Patients were matched by age, gender, comorbidities, record dates, and region to control groups without anorexia or bulimia. Soft tissue injuries were identified through ICD codes, and surgeries were identified through Current Procedural Terminology codes. Differences in relative prevalence were analyzed using chi-square analysis. Patients with anorexia had a significantly increased prevalence of meniscus tears (RR = 1.57, CI 1.22–2.03, p = 0.001) or deltoid ligament sprains (RR = 1.83, CI 1.10–3.03, p = 0.025), and patients with bulimia had a significantly increased prevalence of meniscus tears (RR = 1.98, CI 1.56–2.51, p p p = 0.004), unspecified ankle sprains (RR = 1.56, CI 1.22–1.99, p p = 0.008). Patients with anorexia had a significantly increased prevalence of anterior cruciate ligament reconstructions (RR = 2.83, CI 1.12–7.17, p = 0.037) or any meniscus surgeries (RR = 1.54, CI 1.03–2.29, p = 0.042), and patients with bulimia had a significantly increased prevalence of partial meniscectomies (RR = 1.80, CI 1.26–2.58, p = 0.002) or any meniscus surgeries (RR = 1.83, CI 1.29–2.60, p  Anorexia and bulimia are associated with increased prevalence of soft tissue injuries and surgeries. Orthopedic surgeons should be aware of this risk, and patients presenting to clinics should be informed of the risks associated with these diagnoses and provided with resources promoting recovery to help prevent further injury or surgery.</p

Bordetella pertussis FbpA Binds Both Unchelated Iron and Iron Siderophore Complexes

Bordetella pertussis is the causative agent of whooping cough. This pathogenic bacterium can obtain the essential nutrient iron using its native alcaligin siderophore and by utilizing xeno-siderophores such as desferrioxamine B, ferrichrome, and enterobactin. Previous genome-wide expression profiling identified an iron repressible B. pertussis gene encoding a periplasmic protein (FbpA_Bp). A previously reported crystal structure shows significant similarity between FbpA_Bp and previously characterized bacterial iron binding proteins, and established its iron-binding ability. Bordetella growth studies determined that FbpA_Bp was required for utilization of not only unchelated iron, but also utilization of iron bound to both native and xeno-siderophores. In this <i>in vitro</i> solution study, we quantified the binding of unchelated ferric iron to FbpA_Bp in the presence of various anions and importantly, we demonstrated that FbpA_Bp binds all the ferric siderophores tested (native and xeno) with μM affinity. <i>In silico</i> modeling augmented solution data. FbpA_Bp was incapable of iron removal from ferric xeno-siderophores <i>in vitro</i>. However, when FbpA_Bp was reacted with native ferric-alcaligin, it elicited a pronounced change in the iron coordination environment, which may signify an early step in FbpA_Bp-mediated iron removal from the native siderophore. To our knowledge, this is the first time the periplasmic component of an iron uptake system has been shown to bind iron directly as Fe³⁺ and indirectly as a ferric siderophore complex