Viscosupplementation Is Effective for the Treatment of Osteoarthritis in the Hip: A Systematic Review.

PURPOSE: To assess the efficacy of intra-articular viscosupplementation as a therapeutic intervention for hip osteoarthritis (OA), as well as to assess the duration of efficacy, effect of dose, composition and number of injections of the viscosupplement, and the incidence of adverse effects. METHODS: We performed a systematic review using the literature search from the following databases: Embase, Medline, PubMed, Web of Science, and Scopus. Quality assessment of the included studies was performed using the Modified Newcastle-Ottawa Quality Assessment Scale. Random-effects meta-analysis and mixed-effects subgroup analysis were carried out, but due to the high heterogeneity, low level of evidence, and high risk of bias of the included studies after analyzing the data, weighted means and pooled estimates have not been provided. Instead, we have provided a subjective synthesis of the results. RESULTS: Forty studies were included in the analysis from an initial search of 3,265 studies, with data from a total of 3,350 patients. The level of available evidence was low with an overall high risk of bias. Nearly all studies showed a reduction in mean pain at 1 month, 3 months, and 6 months of follow-up, as well as at the end point, and an improvement in mean patient-reported function was also seen at these time points. However, heterogeneity was extremely high at all time points and remained despite attempts at removing outliers. Subgroup analyses looking at the effects of dose, volume, composition of viscosupplement, and number of injections were carried out, but substantial heterogeneity still remained. There were no lasting adverse effects. CONCLUSIONS: Weak evidence suggests that viscosupplementation improves patient-reported pain and function at end point compared to baseline, regardless of dose, volume, composition, and number of injections. However, due to the high heterogeneity, low level of evidence, and high risk of bias in the current available literature, the strength of our conclusions is limited. LEVEL OF EVIDENCE: Level IV, systematic review of level I to IV studies.

Does Whole-Body Vibration Training Have a Concurrent Effect on Bone and Muscle Health? A Systematic Review and Meta-Analysis.

BACKGROUND: Aging results in musculoskeletal disorders, which are a leading cause of disability worldwide. While conventional nonpharmacological treatments have included interventions such as resistance exercise, there are subgroups of people who may be at risk of exercise-related injuries, for example, falls. Whole-body vibration (WBV) is an intervention that helps improve musculoskeletal function and is viable for those with limited mobility. OBJECTIVES: Whether WBV has a dual effect on bone and muscle conditions remains unknown. We aim to assess the evidence of the effects of WBV on bone and muscle parameters concurrently in older people. METHODS: Under Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, a systematic literature search was performed in MEDLINE, EMBASE, EMCARE, and the Cochrane Central Registry of Controlled Trials. The main outcomes were changes in bone and muscle parameters. RESULTS: Our meta-analysis showed that WBV does not have significant synergistic effects on measured bone (bone mineral density [BMD] in the hip and lumbar spine) and muscle (lean muscle mass and sit-to-stand time) outcomes, compared to controls (i.e., no WBV included). CONCLUSION: While there were no significant results, the included studies are limited by small sample size and variable intervention protocols and follow-up periods. Further trials should endeavor to measure both bone and muscle outcomes concurrently with a longer follow-up time. Osteoporosis status in participants must also be considered as it is not yet possible to exclude that WBV may have a significant effect on BMD in people with known osteoporosis. WBV does not appear to simultaneously influence bone and muscle health in older people, and future research is required to establish a regimen that may lead to measurable clinical efficacy.

The effect of rapamycin and its analogues on age-related musculoskeletal diseases: a systematic review.

BACKGROUND: Preclinical studies have shown a therapeutic role of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1) inhibition with rapamycin and its analogues (rapalogues) on several age-related musculoskeletal disorders (MSKD). However, the applicability to humans of these findings is unknown. OBJECTIVE: To assess the efficacy of rapalogues on age-related MSKD in humans. METHODS: We conducted a systematic review according to the PRISMA guidelines. MEDLINE, EMBase, EMCare, and Cochrane Central Registry of Controlled Trials were searched for original studies examining the effects of rapalogues on outcomes linked to the age-related MSKD in humans. This review is registered in the PROSPERO database (University of New York; registration number CRD42020208167). RESULTS: Fourteen studies met the inclusion criteria and were analyzed. The effect of rapamycin and other rapalogues, including everolimus and temsirolimus, on bone, muscle and joints have been evaluated in humans; however, considerable variability concerning the subjects' age, inclusion criteria, and drug administration protocols was identified. In bone, the use of rapamycin is associated with a decrease in bone resorption markers dependent on osteoclastic activity. In muscle, rapamycin and rapalogues are associated with a reduction in muscle protein synthesis in response to exercise. In the context of rheumatoid arthritis, rapamycin and rapalogues have been associated with clinical improvement and a decrease in inflammatory activity. CONCLUSION: Although there are studies that have evaluated the effect of rapamycin and rapalogues on MSKD in humans, the evidence supporting its use is still incipient, and the clinical implication of these results on the development of osteoporosis, sarcopenia, or osteosarcopenia has not been studied, opening an interesting field for future research.

Left Atrial Appendage Thrombus Detected During Hyperacute Stroke Imaging Is Associated With Atrial Fibrillation.

BACKGROUND AND PURPOSE: Left atrial appendage (LAA) is the likely embolic source in atrial fibrillation (AF)-related cardioembolic strokes. We sought to determine the prevalence of LAA thrombus on hyperacute stroke imaging and its association with AF. METHODS: We retrospectively examined the clinical and radiological features of patients assessed through the hyperacute stroke imaging pathway over a 12-month period at Christchurch Hospital. The LAA was included in the computed tomography angiogram scan-range as part of the multimodal imaging protocol. Two radiological readers blinded to clinical information independently assessed for the presence of LAA thrombus. The association between AF and LAA thrombus was determined by multivariable logistic regression analysis. RESULTS: Of 303 patients included in the analysis, the overall prevalence of LAA thrombus was 6.6% and 14.9% in patients with known AF. Patients with LAA thrombus were older (85 versus 75 years, P<0.01), more commonly had known or newly diagnosed AF (75% versus 30%, P<0.01) and heart failure (30% versus 8%, P=0.01), and was associated with intracranial large vessel occlusion (65% versus 39%, P=0.02). In the multivariable model, AF (odds ratio, 3.71 [95% CI, 1.25-11.01] P=0.02) was independently associated with LAA thrombus after adjusting for age and congestive heart failure. Interrater reliability was moderate (kappa=0.56). CONCLUSIONS: LAA thrombus is a potential radiological marker of AF and can be assessed as a part of hyperacute stroke imaging.

Large anterior temporal Virchow-Robin spaces: unique MR imaging features.

INTRODUCTION: Large Virchow-Robin (VR) spaces may mimic cystic tumor. The anterior temporal subcortical white matter is a recently described preferential location, with only 18 reported cases. Our aim was to identify unique MR features that could increase prospective diagnostic confidence. METHODS: Thirty-nine cases were identified between November 2003 and February 2014. Demographic, clinical data and the initial radiological report were retrospectively reviewed. Two neuroradiologists reviewed all MR imaging; a neuropathologist reviewed histological data. RESULTS: Median age was 58 years (range 24-86 years); the majority (69 %) was female. There were no clinical symptoms that could be directly referable to the lesion. Two thirds were considered to be VR spaces on the initial radiological report. Mean maximal size was 9 mm (range 5-17 mm); majority (79 %) had perilesional T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensity. The following were identified as potential unique MR features: focal cortical distortion by an adjacent branch of the middle cerebral artery (92 %), smaller adjacent VR spaces (26 %), and a contiguous cerebrospinal fluid (CSF) intensity tract (21 %). Surgery was performed in three asymptomatic patients; histopathology confirmed VR spaces. Unique MR features were retrospectively identified in all three patients. CONCLUSION: Large anterior temporal lobe VR spaces commonly demonstrate perilesional T2 or FLAIR signal and can be misdiagnosed as cystic tumor. Potential unique MR features that could increase prospective diagnostic confidence include focal cortical distortion by an adjacent branch of the middle cerebral artery, smaller adjacent VR spaces, and a contiguous CSF intensity tract.

An Unusual Case of Delayed-Onset Rituximab-Induced Ventricular Tachycardia: A Case Report.

Cardiac disease associated with cancer treatment is a common adverse effect that is well-treated with appropriate monitoring. However, some cardiac adverse effects with cancer treatment are not well-understood, in particular rituximab-associated ventricular tachycardia. We present the fourth case of rituximab-associated ventricular tachycardia in a patient who is rituximab-naive and who does not have known cardiac disease history. This patient developed non-sustained polymorphic ventricular tachycardia 14 hours after rituximab was started and 6 hours after it was stopped, and after extensive monitoring including a 30-day event monitor, did not develop further significant runs of ventricular tachycardia.

Type I Brugada Pattern in a Febrile Patient Following COVID-19 Vaccination Booster.

There have been studies published regarding the association between developing Brugada syndrome after an acute COVID-19 infection. In this case, we present a patient who presented with a syncopal episode and subsequently found to have Type I Brugada pattern on electrocardiogram. The patient underwent placement of a single chamber defibrillator. Genetic analysis demonstrated SCN5A variant which is associated with cardiac conditions including Brugada syndrome.

Unusual Urothelial Tumors and Refractory Uremia Due to Balkan Endemic Nephropathy: A Case Report.

Balkan endemic nephropathy (BEN) is a rare progressive chronic renal disease found in residents living along the Balkan peninsula. We present a 92-year-old female who complained initially of cardio-respiratory symptoms and was found to have an acute hypoxemic respiratory failure with hypervolemia. The patient underwent computed tomography imaging and was found to have bilateral pleural effusions and moderate left-sided renal atrophy with left-sided hydronephrosis. The patient underwent diuresis for fluid overload and was treated with broad-spectrum antibiotics for hospital-acquired pneumonia. Further urological work-up revealed masses in the posterior bladder wall and left ureteropelvic junction. A biopsy of the posterior bladder wall mass confirmed high-grade papillary urothelial carcinoma. A review of the epidemiological history revealed the patient lived in Kosovo/former Yugoslavia for several decades following birth. A review of old records revealed the patient had chronic kidney disease (CKD) that was not fully explained by other causes, such as hypertension or diabetes. Given the epidemiological history, accelerated CKD, and unusual locations of urothelial carcinoma, the patient was diagnosed with BEN. Despite medical management and hemodialysis, the patient's renal function and mental status continued to deteriorate, and the decision was made to proceed with palliative care measures.

The Use of Intra-articular Platelet-Rich Plasma as a Therapeutic Intervention for Hip Osteoarthritis: A Systematic Review and Meta-analysis.

BACKGROUND: There is a cohort of patients in whom hip preservation surgery is not indicated, because they have developed signs of early osteoarthritis (OA), and nor can they have a hip replacement, as they are too early in the disease process. Management of this cohort of patients is not standardised and both pharmacological and nonpharmacological measures are utilised to reduce pain. Interventions available for early OA include intra-articular injections of steroids, viscosupplementation and more recently platelet-rich plasma (PRP). However, the use of PRP in hip OA has not yet been studied systematically. PURPOSE: To assess intra-articular PRP as a therapeutic intervention for hip OA, including the duration of efficacy, influence of dose and composition of PRP, and the incidence of adverse effects. STUDY DESIGN: A systematic review and meta-analysis; Level of evidence, 4. METHODS: We performed literature searches on the MEDLINE, EMBASE, CINAHL, WEB OF SCIENCE, COCHRANE, and SCOPUS databases, and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Data were pooled using random-effects meta-analysis. We assessed the quality of the included studies using the methodological index for non-randomized studies instrument, with an additional assessment for randomized controlled trials with the revised Cochrane risk of bias tool for randomized trials. This is the first study to concisely collate the available data on the use of PRP in hip OA. RESULTS: Eight studies were included in the analysis, with data from a total of 331 patients. PRP significantly reduced pain compared with the baseline at multiple time points, with the greatest effect at the 1- to 2-month follow-up, but PRP significantly improved function only at the 1- to 2-month follow-up. A significantly larger reduction in pain was achieved with a single injection of PRP compared with multiple injections, a total injected dose of PRP <15 mL compared with ≥15 mL, and use of a leukocyte-poor PRP preparation compared with leukocyte-rich PRP. There were no lasting adverse effects. CONCLUSION: Low- and moderate-quality evidence suggests that PRP reduces pain and improves function at the end-point follow-up of studies compared with the baseline. Moderate-quality evidence suggests that a larger reduction in pain is achieved with a single injection of PRP compared with multiple injections, and low-quality evidence attributes a larger reduction of pain with a total injected dose of PRP <15 mL compared with ≥15 mL and using leukocyte-poor PRP compared with leukocyte-rich PRP.

Aorta to Right Ventricular Fistula Status Post-TAVR.

Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure that involves replacing a damaged aortic valve using a catheter, typically inserted through a small incision in the leg, leading to faster recovery and reduced risks compared with traditional open-heart surgery. It is a common procedure; however, it is not without adverse events. We report a case of an 83-year-old man who underwent TAVR for the indication of severe symptomatic aortic stenosis. Shortly thereafter, he complained of progressive shortness of breath and was hospitalized for acute on chronic heart failure. Transesophageal echocardiography (TEE) was the first indication of a potential aorta to right ventricular fistula, and this was confirmed by a cardiac computed tomography angiography (CTA). He underwent a period of medical observation but did not do well, requiring re-admission to the hospital for acute on chronic heart failure. He was ultimately treated by percutaneous low-profile shunt closure using a septal occluder device. Percutaneous shunt closure in symptomatic patients using percutaneous low-profile shunt closure devices seems to be the best treatment option in high surgical risk patients.

"It's Not Just Bacteria": A Cavitary Lung Lesion in a Patient Living in the Coachella Valley.

Cavitary pulmonary coccidioidomycosis is rare diagnosis with an incidence of 13% to 15% of pulmonary coccidioidomycosis cases. High clinical suspicion is necessary in the setting of geographical location endemicity. We present a 49-year-old male who has lived in the Coachella Valley of California for several years, with a medical history of uncontrolled type 2 diabetes who noted 1 week of right-sided chest pain with shortness of breath, fever, chills, night sweats, and weight loss. A chest X-ray revealed a 4- to 5-cm mass in the right lung. Initial workup revealed negative sputum cultures (aerobic/anaerobic, acid-fast bacilli). However, dedicated fungal cultures (samples from sputum, lymph nodes, lung right lower lobe bronchial swabs), bronchial washings, and surgical tissue biopsy of the right lower lobe revealed mold. The patient underwent right thoracotomy with right lower lobectomy and right mediastinal lymph node dissection for both diagnostic (lung specimen) and therapeutic (removing necrotic lung tissue, source control) purposes. Finally, serum Coccidioides antigens were positive and antibody titers were positive at 1:8; surgical biopsy of the right lower lobe grew mold that came back positive for Coccidioides posadasii. Targeted pharmacotherapy was commenced using intravenous fluconazole and then oral fluconazole for 3 months was prescribed upon discharge. The patient had gradual improvement of his shortness of breath and was instructed to follow-up at an infectious disease clinic.

Correlation of ACR TI-RADS and Patient Outcomes in a Real-World Cohort Presenting for Thyroid Ultrasonography.

Context: The American College of Radiology Thyroid Image Reporting and Data System (ACR TI-RADS) was developed to predict malignancy risk in thyroid nodules using ultrasound features. TI-RADS was derived from a database of patients already selected for fine-needle aspiration (FNA), raising uncertainty about applicability to unselected patients. Objective: We aimed to assess the effect of ACR TI-RADS reporting in unselected patients presenting for thyroid ultrasound in a real-world setting. Methods: Records for all patients presenting for thyroid ultrasonography in Canterbury, New Zealand, were reviewed across two 18-month periods, prior to and after implementation of TI-RADS reporting. Patient outcomes were compared between the 2 periods. Malignancy rates were calculated for nodules 10 mm or larger with a definitive FNA or histology result. Results: A total of 1210 nodules were identified in 582 patients prior to implementation of TI-RADS; 1253 nodules were identified in 625 patients after implementation of TI-RADS. TI-RADS category was associated with malignancy rate (0% in TR1 and TR2, 3% in TR3, 5% in TR4, 12% in TR5; P = .02); however, 63% of nodules were graded TR3 or TR4, for which malignancy rate did not meaningfully differ from baseline risk. After implementation of TI-RADS there was a small reduction in the proportion of patients proceeding to FNA (49% vs 60%; P < .01) or surgery (14% vs 18%; P < .05), with no difference in cancer diagnoses (3% vs 4%, not significant). Conclusion: TI-RADS category is associated with malignancy rate and may alter clinical decision-making in a minority of patients; however, it is nondiscriminatory in the majority of nodules. In this study of unselected patients, nodules classified as TR5 and thus considered "highly suspicious" for cancer had only a modest risk of malignancy.

Sepsis as the Grand Mimic of Secondary Hemophagocytic Lymphohistiocytosis: Serratia marcescens Bacteremia with Concomitant Decompensated Cirrhotic Liver Disease.

Secondary hemophagocytic lymphohistiocytosis (HLH) is an elusive entity with sequelae that may be confused with sepsis. We discuss a 45-year-old man with decompensated liver cirrhosis with sepsis treated with broad-spectrum intravenous antibiotics. Further work-up initially supported sepsis-HLH overlap syndrome (SHLHOS) and corticosteroids were added. Ongoing refractory hypotension ensued, and the patient passed within 31 hours of presentation. Based on the patient's overwhelming immune activation and clinical course likely unsalvageable by cytotoxic immunosuppressive agents, the patient was diagnosed with sepsis with acute end organ dysfunction. This case report illustrates both the diagnostic challenge of sepsis versus HLH, which both require very different treatments, and the potential for rapid clinical decline without swift recognition and management of the true pathology.

Optimal location for fibular osteotomy to provide maximal compression to the tibia in the management of delayed union and hypertrophic non-union of the tibia.

BACKGROUND: Tibial shaft fractures are the commonest long bone fracture, with early weight-bearing improving the rate of bony union. However, an intact fibula can act as a strut that splints the tibial segments and holds them apart. A fibular osteotomy, in which a 2.5 cm length of fibula is removed, has been used to treat delayed and hypertrophic non-union by increasing axial tibial loading. However, there is no consensus on the optimal site for the partial fibulectomy. METHODS: Nine leg specimens were obtained from formalin-embalmed cadavers. Transverse mid-shaft tibial fractures were created using an oscillating saw. A rig was designed to compress the legs with an adjustable axial load and measure the force within the fracture site in order to ascertain load transmission through the tibia over a range of weights. After 2.5cm-long fibulectomies were performed at one of three levels on each specimen, load transmission through the tibia was re-assessed. A beam structure model of the intact leg was designed to explain the findings. RESULTS: With an intact fibula, mean tibial loading at 34 kg was 15.52 ± 3.26 kg, increasing to 17.42 ± 4.13 kg after fibular osteotomy. This increase was only significant where the osteotomy was performed proximal to or at the level of the tibial fracture. Modelling midshaft tibial loading using the Euler-Bernoulli beam theory showed that 80.5% of the original force was transmitted through the tibia with an intact fibula, rising to 81.1% after a distal fibulectomy, and 100% with a proximal fibulectomy. CONCLUSION: This study describes a novel method of measuring axial tibial forces. We demonstrated that a fibular osteotomy increases axial tibial loading regardless of location, with the greatest increase after proximal fibular osteotomy. A contributing factor for this can be explained by a simple beam model. We therefore recommend a proximal fibular osteotomy when it is performed in the treatment of delayed and non-union of tibial midshaft fractures.

A case report: extensive myocardial calcification and non-ischaemic cardiomyopathy related to past sepsis.

BACKGROUND: Diffuse myocardial calcification following severe sepsis is a rare complication whose long-term effects are not well-understood. CASE SUMMARY: A 51-year-old man presented with a 6-month history of worsening dyspnoea on a background of sepsis 9 years prior. His initial echocardiogram showed moderate systolic dysfunction and a mildly dilated left ventricle. Cardiac computed tomography showed signs of mild coronary artery disease without significant stenosis, but the diffuse extensive left ventricular (LV) mid-myocardial calcification was visible. Cardiac magnetic resonance imaging showed diffuse extensive LV mid-myocardial late gadolinium enhancement in keeping with the calcification. He was diagnosed with non-ischaemic cardiomyopathy. He was commenced on appropriate anti-failure medical therapy, maintains New York Heart Association functional class II functional status, and has received a prophylactic implantable cardioverter-defibrillator. DISCUSSION: Diffuse myocardial calcification might be associated with long-term development of non-ischaemic cardiomyopathy. The benefit of monitoring such patients for long-term effects is not routine, but should be considered.

Does Exercise Influence Kynurenine/Tryptophan Metabolism and Psychological Outcomes in Persons With Age-Related Diseases? A Systematic Review.

BACKGROUND: The kynurenine (KYN) pathway has been implicated in many diseases associated with inflammation and aging ("inflammaging"). Targeting the kynurenine pathway to modify disease outcomes has been trialled pharmacologically, but the evidence of non-pharmacological means (ie, exercise) remains unclear. OBJECTIVE: We aim to assess the evidence of the effects of exercise on the kynurenine pathway and psychological outcomes. METHODS: Under Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, a systematic literature search was performed in MEDLINE, EMBASE, EMCARE, and the Cochrane Central Registry of Controlled Trials. The main outcomes were changes in kynurenine pathway metabolite levels and psychological outcomes. RESULTS: Six studies were analyzed (total n = 379) with exercise demonstrating significant concomitant effects on kynurenine pathway metabolite levels and associated psychological outcomes in domains of somatization, anxiety, and depression. CONCLUSION: Exercise has significant concomitant effect on kynurenine pathway metabolite levels and psychological outcomes. However, clear limitations exist in determining if the changes in the kynurenine pathway can fully explain the changes in psychological outcomes, or whether different diseases and exercise interventions act as confounding factors.

Why do paramedics choose to bring patients to a private emergency department?

OBJECTIVE: While prior experience, favourable location and anticipation of high quality care are known to influence patient choice to attend a private ED, it is likely that decision-making is also influenced by other persons. In particular, patients arriving by ambulance are under the care of paramedics, whose values towards healthcare and rationale for choosing one ED over another have not been studied. This study aimed to describe reasons why paramedics choose to bring patients to a private ED. METHODS: Exploratory, qualitative study using semi-structured, face-to-face interviews with paramedics bringing patients to a private ED from the community. Two primary questions reinforced by structured prompts were asked: 'Why did you choose to come to this emergency department?' and 'What are your general expectations of this emergency department visit?' Interviews were audio recorded, transcribed verbatim and analysed thematically. RESULTS: Fifty paramedics were interviewed with 48 interviews able to be transcribed and used in analysis. Four factors were identified to increase the likelihood of a private ED destination: specific direction, institutional allegiance, hospital logistics and systems and receiving hospital service ethos. CONCLUSIONS: Paramedics take into consideration when possible patient's wishes and are more likely to bring a patient to a private ED if they have specific direction from the patient or the patient's family or GP. The likelihood of presenting to a private ED is increased if the patient has an allegiance with the facility and the paramedics perceive favourably the hospital logistics and systems as well as service ethos.

Contribution of the heme propionate groups to the electron transfer and electrostatic properties of myoglobin.

The role of the heme propionate groups in determining the electron transfer and electrostatic properties of myoglobin have been studied by thermodynamic, kinetic, and spectroscopic studies of horse heart myoglobin in which the heme propionate groups are esterified. Spectroelectrochemical analysis has established that the E(m,7) of dimethylester heme-substituted Mb (DME-Mb) (E(m,7)=100.2(2)mV vs. NHE (Normal Hydrogen Electrode) (25 degrees C) is increased approximately 40mV relative to that of the native protein with DeltaH degrees =-12.9(2) kcal/mol and DeltaS degrees =-51.0(8) cal/mol/deg (pH 7.0, mu=0.1M (phosphate)). The second order rate constant for reduction of DME-metMb by Fe(EDTA)(2-) is increased >400-fold relative to that for reduction of native metMb to a value of 1.34(2)x10(3)M(-1)s(-1) with DeltaS(double dagger)=-13(1) cal/mol/deg and DeltaH(double dagger)=9.2(3) (pH 7.0, micro=0.1M (phosphate)). Analysis of the pH dependences of the reduction potential and rate constant for reduction by Fe(EDTA)(2-) demonstrates that heme propionate esterification introduces significant changes into the electrostatic interactions in myoglobin. These changes are also manifested by differences in the pH dependences of the (1)H NMR spectra of native and DME-metMb that reveal shifts in pK(a) values for specific His residues as the result of heme propionate esterification. In sum, the current results establish that heme propionate esterification not only affects the electron transfer properties of myoglobin but also influences the titration behavior of specific His residues.