Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPARγ.

Neuroinflammation stands as a critical player in the pathogenesis of diverse neurological disorders, with microglial cells playing a central role in orchestrating the inflammatory landscape within the central nervous system. Cannabidiol (CBD) has gained attention for its potential to elicit anti-inflammatory responses in microglia, offering promising perspectives for conditions associated with neuroinflammation. Here we investigated whether the NLRP3 inflammasome and inducible nitric oxide synthase (iNOS) are involved in the protective effects of CBD, and if their modulation is dependent on cannabinoid receptor 2 (CB2) and PPARγ signalling pathways. We found that treatment with CBD attenuated pro-inflammatory markers in lipopolysaccharide (LPS)-challenged BV2 microglia in a CB2- and PPARγ-dependent manner. At a molecular level, CBD inhibited the LPS-induced pro-inflammatory responses by suppressing iNOS and NLRP3/Caspase-1-dependent signalling cascades, resulting in reduced nitric oxide (NO), interleukin-1ß (IL-1ß), and tumour necrosis factor-alpha (TNF-α) concentrations. Notably, the protective effects of CBD on NLRP3 expression, Caspase-1 activity, and IL-1ß concentration were partially hindered by the antagonism of both CB2 receptors and PPARγ, while iNOS expression and NO secretion were dependent exclusively on PPARγ activation, with no CB2 involvement. Interestingly, CBD exhibited a protective effect against TNF-α increase, regardless of CB2 or PPARγ activation. Altogether, these findings indicate that CB2 receptors and PPARγ mediate the anti-inflammatory effects of CBD on the NLRP3 inflammasome complex, iNOS activity and, ultimately, on microglial phenotype. Our results highlight the specific components responsible for the potential therapeutic applications of CBD on neuroinflammatory conditions.

Two-Year Survivorship and Patient-Reported Outcomes of a Prospectively Enrolled Cohort of INFINITY Total Ankle Arthroplasties.

BACKGROUND: The INFINITY total ankle implant is a widely and successfully used option for total ankle arthroplasty. The purpose of this study is to assess the 2-year survivorship, complication rates, patient-reported outcomes, and radiologic findings of prospectively enrolled patients undergoing a fixed-bearing total ankle arthroplasty (TAA). This study sought to determine if factors such as traditional vs patient-specific instrumentation, preoperative degree of arthritis, deformity, or etiology of arthritis impact surgical or clinical outcomes. METHODS: A total of 143 prospectively enrolled patients (148 ankles) underwent TAA with a fixed-bearing total ankle implant between 2017 and 2019 at 9 different institutions by 9 different surgeons. A total of 116 completed 2-year follow-up. Patients were stratified by instrumentation used, degree of preoperative deformity, the Canadian Orthopaedic Foot and Ankle Society (COFAS) grading system, and etiology of arthritis. Outcomes used included implant survivorship and adverse events within 2 years of surgery. Additionally, patient-reported outcomes and radiographs were collected at 6-month, 1-year, and 2-year postoperatively. PROMs used included Ankle Osteoarthritis Score (AOS), Patient-Reported Outcomes Measurement Information System (PROMIS) global health score, the Foot and Ankle Outcome Score (FAOS), and patient satisfaction (rated from excellent to poor). RESULTS: Implant survivorship at 2 years was 97.79%. There were 17 reoperations (11.5%), with 4 of the implants requiring revision (2.7%). Significant improvements in all PROMs were observed among all subgroups at all postoperative time points without significant variation between subgroups. Patients classified as COFAS type 2 arthritis preoperatively demonstrated significantly more improvement in FAOS Total Symptom Score at the 1- and 2-year measurements than COFAS type 3 patients at both time points. CONCLUSION: Total ankle arthroplasty with a fixed-bearing implant system is a safe and reliable treatment option for patients with end-stage arthritis regardless of degree of deformity or COFAS grading. LEVEL OF EVIDENCE: Level II, prospective cohort study.

High-Pressure Injection Injuries of the Hand in Community and Industrial Settings: Incidence and Trends.

BACKGROUND: High-pressure injection injuries to the hand have been reported in both the community and industrial setting with varying levels of severity. However, there are little epidemiologic data regarding the prevalence of pressure-injection injuries. The purpose of this study is thus to describe trends in emergency department (ED) encounters associated with pressure injection injuries, thereby informing potential investments in research and education for these injuries. METHODS: The National Electronic Injury Surveillance System (NEISS), a nationally representative database of all ED encounters, was queried for all high-pressure injection injuries from 2012 to 2021. Patient demographic and injury data were collected and analyzed to describe trends in incidence, patient demographics, and sequelae of hand injury associated with an ED encounter for a pressure injection-related injury. RESULTS: There were an estimated 15 307 (95% confidence interval: 15 051-15 562) high-pressure injection hand injuries from 2012 to 2021. Injuries were more frequent on weekends with the highest incidence on Sundays (18.9%) and Saturdays (18.0%) and during late spring and summer months (58.6%), with peak incidence occurring in May (16.8%). High-pressure paint injuries demonstrated a significantly higher rate of infection (23.7% of injuries) than pressure washer injuries (3.7%); however, pressure washer injuries were much more common overall (90% vs 10%). CONCLUSION: High-pressure injection injuries to the hand and upper extremity represent a particularly concerning injury mechanism. Prompt recognition and proper management are crucial for improving outcomes. People that utilize pressure washers for household projects should be aware of the risks associated with these machines and utilize proper safety techniques.

Preoperative Opioid Therapy Correlated With Increased Rate of Complications in Foot and Ankle Surgery.

BACKGROUND: The purpose of this study is to determine whether patients with a history of preoperative opioid use will have an increased likelihood of postoperative opioid use and complications after undergoing forefoot, hindfoot, or ankle surgery. METHODS: A retrospective review was conducted on forefoot, hindfoot, and ankle surgeries between 2015 and 2020 with a single fellowship-trained orthopaedic foot and ankle surgeon at an academic medical center. A total of 326 patients (356 feet) were included with a mean follow-up up of 2.12 (range, 1.00-4.98) years. Data collected included demographics, medical comorbidities, treatment history, complications and reoperation rates, patient-reported outcome measures (eg, Foot and Ankle Outcome Score), and opioid exposure. RESULTS: There were significantly more complications among opioid exposed patients than opioid naïve ones (exposed = 29.41%, naïve = 9.62%; P = .044). Preoperative opioid exposure significantly correlated with postoperative opioid exposure (90-day: r = .903, p < .001; 180-day: r = .805, p < .001), and increased hospital length of stay (r = .263, p = .029). Furthermore, body mass index was a significant predictor of postoperative opioid exposure (90-day: r = .262, p = .013; 180-day: r = .217, p = .021), as was concomitant mental illness (90-day: r = .225, p = .035). CONCLUSION: Patients with preoperative opioid exposure have significantly more complications and increased postoperative opioid exposure after foot and ankle surgery. LEVELS OF EVIDENCE: Level III: Retrospective cohort study.

Preoperative Opioid Use Predicts Poorer Outcomes of Total Ankle Arthroplasty and Hindfoot Fusions.

BACKGROUND: This study aimed to determine the impact of preoperative opioid use on outcomes of patients undergoing ankle or hindfoot arthrodesis, or total ankle arthroplasty (TAA). METHODS: We conducted a retrospective review of 190 patients undergoing an ankle or hindfoot arthrodesis (n=122) or TAA (n=68) between December 2015 and September 2020 with a single fellowship-trained orthopaedic foot and ankle surgeon at an academic medical center. Data collected included demographics, medical comorbidities, treatment history, complications and reoperation rates, patient-reported outcome measures (PROMs) (eg, Foot and Ankle Outcome Score [FAOS]), and opioid use. RESULTS: Patients with preoperative opioid use were more likely to continue usage at 90 (r = 0.931, P < .001) and 180 (r = 0.940, P < .001) days postoperatively. For the entire cohort, complication and reoperation rates were 48.9% and 13.2%, respectively. While preoperative opioid use groups did not differ in the overall complication rate, users had significantly more infections (user = 12.5%, nonuser = 3.3%; P = .036) and reoperations (user = 22.5%, nonuser = 10.7%; P = .049). When analyzing postoperative opioid prescriptions, there were many significant correlations with preoperative PROMs, mainly FAOS, such that increased postoperative opioid use was associated with worse subjective outcomes. CONCLUSION: Preoperative opioid users are more likely to continue postoperative opioid use, experience infections, and undergo reoperations. LEVEL OF EVIDENCE: Level III: Retrospective cohort study.

Risks of Chronic Preoperative Opioid Use on Distal Radius Surgery Outcomes.

BACKGROUND: The purpose of this study was to determine the influence of chronic preoperative opioid use on complications, reoperation rates, and postoperative opioid use among patients undergoing open reduction and internal fixation (ORIF) of distal radius fractures. METHODS: A retrospective review of 111 patients who underwent ORIF of a distal radius fracture from 2019 to 2021 at an academic medical center by the same fellowship-trained orthopedic hand surgeon was conducted. Patient demographics, medical comorbidities, perioperative details, surgical complications, and patient-reported outcome measures were analyzed. The SCRIPTS database was used to obtain opioid prescription data. RESULTS: A total of 10 patients (9.01%) were identified as preoperative chronic opioid users. This group was not associated with risk of increased complication. However, they were more likely to continue using narcotics at 90 and 180 days postoperatively. Patients with a history of substance use were at an increased risk of hardware complications and prolonged postoperative pain. In addition, these patients were more likely to receive narcotics at 90 and 180 days, and to have more refills postoperatively. CONCLUSION: Patients with preoperative opioid use are not at an increased risk of surgical complication following ORIF of distal radius fractures. However, they are at an increased risk of prolonged postoperative opioid use. Patients with a known history of substance use were at an increased risk of hardware complications, prolonged pain, and increased postoperative opioid use. Surgeons should consider these associations to better manage individual patients in the postoperative period.

Constraining the Nuclear Symmetry Energy with Multimessenger Resonant Shattering Flares.

Much effort is devoted to measuring the nuclear symmetry energy through neutron star (NS) and nuclear observables. Since matter in the NS core may be nonhadronic, observables like radii and tidal deformability may not provide reliable constraints on properties of nucleonic matter. By performing the first consistent inference using ensembles of core and crust equations of state from astrophysical and nuclear data, we demonstrate that coincident timing of a resonant shattering flare (RSF) and gravitational wave signal during binary NS inspiral probes the crust-core transition region and provides constraints on the symmetry energy comparable to terrestrial nuclear experiments. We show that nuclear masses, RSFs, and measurements of NS radii and tidal deformabilities constrain different density ranges of the equation of state, providing complementary probes.

Preoperative Hypoalbuminemia Not Associated With Total Ankle Arthroplasty Outcomes.

BACKGROUND: This study aims to investigate the effect of hypoalbuminemia on the rates of 30-day complication, readmission, and reoperation following total ankle arthroplasty (TAA). METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2007 to 2019 to identify 710 TAA patients. Patients were then stratified into normal (n = 673) or low (n = 37) albumin groups. Demographics, medical comorbidities, concomitant procedures, hospital length of stay, and 30-day complication, readmission, and reoperation rates were compared between groups. Preoperative serum albumin level was also used as a continuous variable when analyzing postoperative outcomes. RESULTS: The overall cohort was predominantly male (51.5%), and the mean age was 65.02 (range, 45-87) years. We found there to be no statistically significant difference in demographics between cohorts. However, hypoalbuminemia patients were significantly more likely to use long-term steroids for a chronic condition (normal = 6.1%, low = 18.9%; P = .009). Additionally, there was no difference in 30-day complication (normal = 3.0%, low = 0.0%; P = .618), readmission (normal = 2.4%, low = 0.0%; P = .632), and reoperation (normal = 1.0%, low = 0.0%; P = 1.000) rates between groups. CONCLUSION: The results of this study show that malnourished patients are not at an increased risk of 30-day complication, readmission, or reoperation following TAA despite having a worse preoperative comorbidity profile. LEVEL OF EVIDENCE: Level III, Retrospective cohort study.

Long-Term Oral Steroid Use: A Unique Risk Factor in 4-Corner Fusion Compared With Other Wrist Salvage Operations.

INTRODUCTION: Salvage procedures such as proximal row carpectomy, 4-corner fusion, total wrist arthroplasty, and total wrist arthrodesis are commonly used at the end stages of wrist arthritis. These operations have high complication rates, and significant controversy exists regarding the selection of procedure. Long-term oral glucocorticoid therapy has previously been identified as a risk factor for complications in multiple orthopedic procedures. The purpose of this study is to investigate the effect long-term oral preoperative corticosteroid use has on complications after different salvage operations for wrist arthritis. METHODS: The National Surgical Quality Improvement Program database was queried to identify patients who underwent proximal row carpectomy, 4-corner fusion, total wrist arthroplasty, or total wrist fusion between 2005 and 2020. Patients were classified by steroid use. Univariate analysis and multivariate logistic regression were used to assess the risk of complications. RESULTS: A total of 1298 patients were identified. Overall, steroid use was found to be independently associated with a higher complication rate. On multivariate analysis of patients who underwent 4-corner fusion, steroid use was found to be associated with higher complication rate and surgical site infection rate. Steroid use was not associated with increased complications in patients who underwent proximal row carpectomy, total wrist arthroplasty, or total wrist fusion when examined individually. CONCLUSION: Long-term oral corticosteroid therapy was associated with an increased risk of postoperative infections in patients who underwent 4-corner fusion, which was not found in other wrist salvage operations.

Low Preoperative Albumin Associated With Increased Risk of Superficial Surgical Site Infection Following Midfoot, Hindfoot, and Ankle Fusion.

BACKGROUND: This study investigates the effect of malnutrition, defined by hypoalbuminemia, on rates of complication, readmission, reoperation, and mortality following midfoot, hindfoot, or ankle fusion. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried from 2005 to 2019 to identify 500 patients who underwent midfoot (n = 233), hindfoot (n = 261), or ankle (n = 117) fusion. Patients were stratified into normal (n = 452) or low (n = 48) albumin group, which was defined by preoperative serum albumin level <3.5 g/dL. Demographics, medical comorbidities, hospital length of stay (LOS), and 30-day complication, readmission, and reoperation rates were compared between groups. The mean age of the cohort was 58.7 (range, 21-89) years. RESULTS: Hypoalbuminemia patients were significantly more likely to have diabetes (P < .001), be on dialysis (P < .001), and be functionally dependent (P < .001). The LOS was significantly greater among the low albumin group (P < .001). The hypoalbuminemia cohort also exhibited a significantly increased likelihood of superficial infection (P = .048). Readmission (P = .389) and reoperation (P = .611) rates did not differ between the groups. CONCLUSION: This study shows that malnourished patients have an increased risk of superficial infection following foot and ankle fusions but are not at an increased risk of readmission or reoperation, suggesting that low albumin confers an elevated risk of surgical site infection. LEVELS OF EVIDENCE: Level III, Retrospective cohort study.

National incidence and trends of bicycle injury.

Bicycle utilization continues to increase annually, and this trend was recently accelerated by the coronavirus disease of 2019 pandemic. There is limited epidemiologic data, however, regarding the prevalence and nature of bicycle-related injuries. Therefore, the purpose of this study is to characterize trends in bicycle-related injuries. The National Electronic Injury Surveillance System was queried for bicycle-related injuries from 2012 to 2021. Patient demographic and injury data were collected and analyzed to describe trends in incidence, patient demographics, and injury patterns associated with an emergency department encounter for a bicycle-related injury. There were an estimated 4,666,491 (95% confidence interval: 4,661,472-4,671,510) bicycle-related injuries from 2012 to 2021. The incidence of these injuries has significantly decreased over time (R = -0.983, R2 = 0.967, p < 0.001). However, the rate of injury in elderly patients increased over time. Injuries occurred most often during summer months (36%) and on weekend days (31.9%). Males and younger patients were more commonly injured. Head injuries were the most commonly affected body part among all age groups. Fractures were the most common injury type overall. Upper extremity injuries were more common than the lower extremity. Despite increased public bicycle utilization, there is a significant downtrend in bicycle-related injuries over the last decade. Injuries among elderly patients are becoming more common, who demonstrate a high rate of fracture and head injury. Fractures and head injuries were the most common injuries among all age groups, highlighting the importance of bicycle safety initiatives and helmet-wearing regardless of age.

Perilunate Dislocations: Reduction and Stabilization.

Background: The all-dorsal scapholunate reconstruction technique is indicated for the treatment of scapholunate injuries in cases in which the carpus is reducible and there is no arthrosis present. The goal of this procedure is to reconstruct the torn dorsal portion of the scapholunate ligament in order to stabilize the scaphoid and lunate. Description: A standard dorsal approach to the wrist, extending from the third metacarpal distally to the distal radioulnar joint, is utilized. The extensor pollicis longus is transposed and retracted radially, and the second and fourth extensor compartments are retracted ulnarly. A Berger ligament-sparing capsulotomy is utilized to visualize the carpus. Volarly, an extended open carpal tunnel release is also utilized to relieve any median nerve compression and to aid in reduction. The contents of the carpal tunnel can be retracted radially, allowing for visualization of the carpal bones. Joystick pins are placed in order to reduce the scaphoid and lunate. Reduction is held provisionally by clamping the pins until 4 pins can be placed across the carpal bones. For scapholunate reconstruction, 3 holes are made: in the lunate, proximal scaphoid, and distal scaphoid. Suture tape is then utilized to hold the scaphoid and lunate in their proper position. The dorsal wrist capsule and extensor retinaculum are repaired during closure. The pins are cut near the skin and are removed in 8 to 12 weeks. Alternatives: Several other methods of scapholunate reconstruction have been described, including capsulodesis, tenodesis, and bone-tissue-bone repairs. Additionally, in patients who are poor candidates for scapholunate reconstruction, wrist-salvage procedures can be utilized as the primary treatment. Rationale: Scapholunate reconstruction has the advantage of preserving the native physiologic motion of the wrist, in contrast to the many different wrist-salvage procedures that include arthrodesis or arthroplasty. Avoiding arthrodesis is specifically advantageous in patients who have not yet developed arthrosis of the wrist bones. Expected Outcomes: Outcomes of scapholunate reconstruction vary widely; however, there is a nearly universal decrease in range of motion and strength of the wrist. Wrist range of motion is typically 55% to 75% of the contralateral side, and grip strength is typically approximately 65% of the contralateral side. In a prior study, 50% to 60% of patients whose work involved physical labor were able to return to their same level of full-time work. Disabilities of the Arm, Shoulder and Hand scores average between 24 and 30. Specific patients at risk for inferior outcomes are those with delayed surgical treatment, poor carpal alignment following reduction, or open injuries. Important Tips: Patients are counseled preoperatively regarding the likelihood of permanent wrist stiffness and the possibility of scapholunate diastasis even in the setting of technically successful repair.Traction and dorsally directed pressure on the lunate through an extended carpal tunnel incision can aid in reduction of the lunate.The joystick pin position in the dorsal scaphoid is angulated from distal to proximal and that in the lunate is angulated from proximal to distal in order to help correct flexion of the scaphoid and extension of the lunate by clamping together the Kirschner wires. Modifying the distance of the clamp from the carpus can allow precision in the degree of scapholunate angle fixation.Intercarpal Kirschner wire fixation of the scapholunate, lunotriquetral, and midcarpal joints (scaphocapitate and triquetrohamate) is best performed with 0.062-in (1.6-mm) Kirschner wires. The insertion angle is best visualized when the Kirschner wire is introduced from inside the incision through the skin, "inside out," in order to best envision the trajectory on the dorsal carpus and define the starting point on the bone. The Kirschner wire is then advanced through the carpus from outside-in at a slightly more volarly translated (but not angulated) position. The Kirschner wires are then cut beneath the skin at a depth that will allow them to be retrieved but will not cause them to become exposed once swelling decreases.The wrist is generally immobilized until the pins are removed at 3 months postoperatively. Acronyms and Abbreviations: ROM = range of motionK-wire = Kirschner wireDASH = Disabilities of the Arm, Shoulder and HandDISI = dorsal intercarpal ligament instability.

Risk Factors for 30-Day Complications and Unplanned Reoperation Following Surgical Treatment of Distal Radius Fractures.

BACKGROUND: The purpose of this study was to identify demographic data, medical comorbidities, and perioperative factors that are associated with increased risk of overall surgical complications, wound complications, and reoperation within 30 days of open reduction and internal fixation (ORIF) of distal radius fractures. METHODS: All adult patients undergoing ORIF of distal radius fractures in the National Surgical Quality Improvement Program database between 2005 and 2020 were identified. Patients were excluded for secondary procedures, open/infected injuries, or inpatient surgical setting. Demographic data, medical comorbidities, and perioperative data were examined for each patient, and patients were grouped by the presence or absence of any surgical complication. Univariate analysis and multivariate logistic regression were used to identify risk factors. RESULTS: A total of 20 301 patients from between 2005 and 2020 met the inclusion criteria, of which 219 complications (1.1% of cases) were identified. Following multivariate analysis, independent risk factors found to be associated with surgical complications included male sex, smoking, heart failure, longer operative time, and American Society of Anesthesiologists (ASA) classification of 3 or higher. CONCLUSION: Male sex, smoking, heart failure, prolonged operative time, and ASA status of 3 or higher are associated with an increased risk of surgical complications following ORIF of distal radius fractures. These complications, with the exception of heart failure, were also associated with an increased risk of wound complications. Finally, male sex, nonwhite race, smoking, dialysis, prolonged operative time, and 3 or higher ASA class were associated with reoperations. Understanding these risk factors allows surgeons to better predict and prevent complications in high-risk populations.

Pumpkin carving knife injuries: National incidence and trends of hand injury.

INTRODUCTION: Seasonal media reports often describe the dangers of pumpkin carving, yet little data exists regarding the actual incidence of hand injuries resulting from pumpkin carving. The purpose of this study is to describe, quantify, and trend ED encounters associated with pumpkin-related knife injuries. METHODS: The National Electronic Injury Surveillance System (NEISS) was queried for pumpkin-related knife injuries from 2012 to 2021. Patient demographic and injury data was collected and analyzed to describe trends in incidence, patient demographics, and injury patterns associated with an ED encounter for a pumpkin-related knife injury. RESULTS: There were an estimated 20,579 (95% CI: 17,738-23,420) pumpkin-related knife injuries from 2012 to 2021. The incidence of pumpkin-related knife injuries remained stable over time (R2 = 0.195, P = 0.201). Hand injuries comprised 87.6% of all injuries, with the thumb (33.5%) and index finger (25.0%) most commonly affected. Men and women were injured at similar rates (51.6% vs 48.4%). The most common demographic injured were 10 to 19-year olds (31.5%) followed by children <10-years old (19.5%). Women ages 10 to 19-years old were the most commonly injured subgroup (10.0% of all injuries). Most ED presentations occurred on Saturdays (16.5%) or Sundays (23.3%). The large majority occurred during the months of October (83.5%) followed by November (11.2%), with almost half of all cases (45.6%) occurring in the last week of October. Peak incidence of injury occurred on October 30th. CONCLUSION: Pumpkin-related knife injuries are a preventable cause of hand injury with predictably high-incidence in fall months. Additionally, our data suggests further precautions should be taken to prevent injury in pediatric patients. Understanding at-risk populations in addition to implementing public safety initiatives and education on safe pumpkin-carving techniques could prevent serious injuries in the future.

Nitrogenase Chemistry at 10 Kelvin─Phototautomerization and Recombination of CO-Inhibited α-H195Q Enzyme.

CO-bound forms of nitrogenase are N2-reduction inhibited and likely intermediates in Fischer-Tropsch chemistry. Visible-light photolysis at 7 K was used to interrogate all three known CO-related EPR-active forms as exhibited by the α-H195Q variant of Azotobacter vinelandii nitrogenase MoFe protein. The hi(5)-CO EPR signal converted to the hi-CO EPR signal, which reverted at 10 K. FT-IR monitoring revealed an exquisitely light-sensitive "Hi-2" species with bands at 1932 and 1866 cm-1 that yielded "Hi-1" with bands at 1969 and 1692 cm-1, which reverted to "Hi-2". The similarities of photochemical behavior and recombination kinetics showed, for the first time, that hi-CO EPR and "Hi-1" IR signals arise from one chemical species. hi(5)-CO EPR and "Hi-2" IR signals are from a second species, and lo-CO EPR and "Lo-2" IR signals, formed after prolonged illumination, are from a third species. Comparing FT-IR data with CO-inhibited MoFe-protein crystal structures allowed assignment of CO-bonding geometries in these species.

No effect of preoperative ulceration on outcomes of tibiotalocalcaneal arthrodesis.

BACKGROUND: Tibiotalocalcaneal (TTC) arthrodesis is a commonly performed operation for complex hindfoot pathology, but the effect of preoperative ulceration on TTC outcomes has been debated. This study aims to examine infection rates in patients undergoing TTC arthrodesis with internal fixation with and without concomitant hindfoot ulceration. METHODS: We conducted a retrospective review of 31 patients who underwent a TTC arthrodesis between June 2016 and February 2021 with a fellowship-trained foot and ankle surgeon at an academic medical center. Nine (29.0%) patients had preoperative ulceration. Mean follow-up duration was 1.49 (range, 0.51-4.28) years. Other data collected included demographics, comorbidities, surgical approach, fixation method, and complication and reoperation rates. RESULTS: There was no difference in overall complication (ulcer [U]=66.7%, no ulcer [NU]=50.0%; p = .397), infection (U=33.3%, NU=31.8%; p = .935), or reoperation (U=55.6%, NU=27.3%; p = .135) rates between groups. CONCLUSIONS: TTC arthrodesis with internal fixation appears to be a reasonable treatment method for patients with a preoperative ulcer.

Carbon monoxide binding to α-R277H Mo-nitrogenase - Evidence for multiple pH-dependent species from IR-monitored photolysis.

The nitrogenase (N2ase) enzyme family is responsible for the conversion of dinitrogen into biologically accessible ammonia, a critical step in the global nitrogen cycle. Carbon monoxide (CO) has long been known as an inhibitor of dinitrogen reduction, but it can also be reduced to hydrocarbons catalyzed by all three N2ases, namely the wild-type Mo enzyme and select variants and the V and Fe nitrogenases, both of which are orders of magnitude more effective. CO interactions with N2ases are thus relevant to both dinitrogen fixation and Fischer-Tropsch-like chemistry. Here, we investigated the interaction of CO with the α-R277H variant of the Azotobacter vinelandii N2ase MoFe protein, in which the α-subunit 277Arg residue is replaced by His and results in production of only the S = 3/2 EPR signal (denoted as hi(5)-CO). Fourier-transform infrared (FT-IR) spectroscopy was used to follow the photolysis of CO bound to the α-R277H variant under cryogenic conditions. Multiple EPR-silent species were observed with FT-IR spectroscopic signatures previously assigned to CO-inhibited forms of the α-H195Q and α-H195N N2ase variants. The distribution of these CO-inhibited forms varied dramatically with pH over the range of pH 6.5 to pH 8.5, indicating protonation/deprotonation involvement.

A Late Diagnosis of Transthyretin Amyloidosis.

Cardiac amyloidosis is a rare disease caused by the accumulation of protein-based fibrils that deposit into the myocardium, causing disease. The accumulation of amyloid in the heart tissue causes the heart to become increasingly stiff, reducing compliance, with the eventual decline of the heart's systolic function over time as the disease progresses. The restrictive physiology of the disease usually prompts investigation; however, if allowed to progress, the systolic function becomes affected in the later stages of the disease. We present a case of late-stage transthyretin-related amyloidosis (ATTR).

A novel fast-acting sub-perception spinal cord stimulation therapy enables rapid onset of analgesia in patients with chronic pain.

Background: Treating chronic pain using sub-perception Spinal Cord Stimulation (SCS) does not elicit paresthesia but is associated with long analgesic 'wash-in' (i.e. duration until maximum pain relief) and prolonged assessment of therapy. We describe the attainment of clinically meaningful and rapid-onset analgesic outcomes using a novel sub-perception SCS approach.Methods: This observational case-series evaluated patients implanted with an SCS device for chronic pain, who underwent re-programming utilizing a new methodology in which paresthesia was used to guide sub-perception stimulation field targeting at specific parameters including charge-balanced symmetrical pulses at 90 Hz (termed Fast-Acting Sub-Perception Therapy, FAST). Pain scores (NRS) were collected as reported per standard-of-care from patient charts.Results: Mean overall pain score at baseline was 8.4 ± 0.2 (n = 41). After activation of FAST, a 7.1-point reduction in overall pain score was (1.3 ± 0.2, p < 0.0001) reported within 11.2 ± 1.9 minutes (n = 34). This decrease in pain score was sustained out to 3-month (1.6 ± 0.3, n = 26) and 6-month follow-up (1.7 ± 0.4, n = 18). At last follow up (mean = 223 ± 132 days), a pain score of 1.6 ± 0.3, n = 30 was determined.Conclusions: After FAST implementation, a profound analgesic response, requiring substantially less energy than conventional sub-perception methodologies, was observed. This rapid analgesic onset achieved with the novel FAST technique suggests the potential for an alternative mechanism of action(s) of sub-perception SCS.

Why Aquinas's Metaphysics of Gender Is Fundamentally Correct: A Response to John Finley.

In an important article, John Finley suggests a correction to Aquinas's understanding of gender distinction. Disagreeing with Aquinas, Finley proposes that gender distinction (male and female) stems from the soul rather than from the body. In this essay, I will show that this is not a tenable position because it does not fit with either what we know about the physical development of sex differences or the unity of man and woman as a single human species. I will defend Aquinas's fundamental insights into the root of gender distinction without defending his biological understanding of the process itself. I will argue that there is a single generic generative power in the soul that is determined by the matter to which the soul is united, to be expressed as either male or female. This paradigm, I believe, copes better than the one offered by Finley with phenomena such as intersexed persons and sex reassignment surgery. While I do not accept the idea of a feminine or masculine soul, the paradigm offered here does lead to the notion of the soul being feminized or masculinized on account of the matter that it informs.