Same-Day Discharge Total Hip and Knee Arthroplasty: Trends, Complications, and Readmission Rates.

BACKGROUND: Although total hip arthroplasty (THA) and total knee arthroplasty (TKA) are transitioning to surgery centers, there remain limited data on trends, comorbidities, and complications in patients discharged the same day of surgery. In addition, many studies are limited to the Medicare population, excluding a large proportion of outpatient surgery patients. METHODS: Primary, elective THA/TKA cases between 2010 and 2017 were retrospectively identified using the PearlDiver All-Payer Database and separated based on surgery as well as same-day discharge (SDD) or non-SDD. Data were collected on demographics, rates, comorbidities, and complications. Multivariable logistic regression determined adjusted odds ratios (ORs) for 90-day complications requiring readmission for each group. RESULTS: In total, 1,789,601 (68.8% TKA, 31.2% THA) patients were identified where 2.9% of TKAs and 2.2% of THAs were SDD. Annual SDD rates are increasing, with a 15.8% mean annual change for SDD-THA and 11.1% for SDD-TKA (P < .001). SDD patients were younger with fewer comorbidities (P < .001). Regression analysis showed an overall slightly higher OR of complications requiring readmission for SDD-TKA vs non-SDD-TKA (OR 1.14, 95% confidence interval [CI] 1.07-1.21, P < .001). There was no significant difference for SDD-THA vs non-SDD-THA (OR 1.03, 95% CI 0.94-1.13, P = .49). In univariate analysis, SDD-THA vs SDD-TKA had more mechanical complications (P < .001), but less pulmonary embolisms (P < .001). Regression analysis showed a slightly higher risk of complications for SDD-THA vs SDD-TKA (OR 1.19, 95% CI 0.99-1.44, P = .05). CONCLUSION: The prevalence of SDD is rising. SDD-THA is increasing more rapidly than SDD-TKA. SDD patients are generally younger with fewer comorbidities. SDD-TKA has slightly higher odds of complications requiring readmission than non-SDD-TKA. SDD-THA and SDD-TKA have different complication profiles.

Temporary new implant spacers increase post-reimplantation total knee prosthesis survival after periprosthetic joint infection.

PURPOSE: Two-stage exchange arthroplasty is considered the gold standard for treatment of periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). Antibiotic cement spacers can include cement-based spacers (CBS), new components (NEW), and autoclaved components (ACL). The factors that most influence post-reimplantation prosthesis (PRP) survival were determined. METHODS: A retrospective database review of patients undergoing two-stage exchange arthroplasty from 2008 to 2014 was performed. There were 85 patients, 25 patients and 30 patients in CBS, NEW and ACL groups, respectively. Patient, disease and surgical characteristics were collected and analyzed. Post-reimplantation prosthesis (PRP) survival was modeled using the Kaplan-Meier method. Cox proportional hazard modeling was then performed to identify risk factors associated with implant failure. RESULTS: Overall PRP survival was 82% in 140 unilateral TKAs. PRP survival between groups was 81%, 96% and 73% within the minimum 2-year follow-up period, respectively. There was a difference in median interval-to-reimplantation between groups (CBS, 72.0 days; NEW, 111.0 days; ACL, 84.0 days, p = 0.003). Adjusting for time-to-reimplantation, NEW spacers demonstrated greater PRP survival compared with ACL spacers (p = 0.044), and a trend towards greater survival compared with CBS spacers (p = 0.086). Excluding early failures (< 90 days), NEW spacers still demonstrated greater survival than ACL spacers (p = 0.046). Lower volume (≤ 10 within this series) surgeons tended to use more CBS spacers, while higher volume surgeons were comfortable with ACL spacers. CONCLUSIONS: There was greater PRP survival with NEW spacers. NEW spacers also demonstrated an increased inter-stage interval, likely because of increased comfort and motion. There were spacer choice differences between low- and high-volume surgeons. LEVEL OF EVIDENCE: III.

The James A. Rand Young Investigator's Award: Are Intraoperative Cultures Necessary If the Aspiration Culture Is Positive? A Concordance Study in Periprosthetic Joint Infection.

BACKGROUND: The concordance between preoperative synovial fluid culture and multiple intraoperative tissue cultures for identifying pathogenic microorganisms in periprosthetic joint infection (PJI) remains unknown. Our aim is to determine the diagnostic performance of synovial fluid culture for early organism identification. METHODS: A total of 363 patients who met Musculoskeletal Infection Society criteria for PJI following primary total joint arthroplasty were identified from a retrospective joint infection database. Inclusion criteria required a positive preoperative intra-articular synovial fluid sample within 90 days of intraoperative tissue culture(s) at revision surgery. Concordance was defined as matching organism(s) in aspirate and intraoperative specimens. RESULTS: Concordance was identified in 279 (76.8%) patients with similar rates among total hip arthroplasties (77.2%) and total knee arthroplasties (76.4%, P = .86). Culture discordance occurred in 84 (23.1%) patients; 37 (10.2%) had no intraoperative culture growth and 33 (90.1%) were polymicrobial. Monomicrobial Staphylococcal PJI cases had high sensitivity (0.96, 95% confidence interval [CI] 0.92-0.98) and specificity (0.85, 95% CI 0.80-0.90). Polymicrobial infections had the lowest sensitivity (0.06, 95% CI 0.01-0.19). CONCLUSION: Aspiration culture has favorable sensitivity and specificity when compared to tissue culture for identifying the majority of PJI organisms. Clinicians can guide surgical treatment and postoperative antibiotics based on monomicrobial aspiration results, but they should strongly consider collecting multiple tissue cultures to maximize the chance of identifying an underlying polymicrobial PJI. LEVEL OF EVIDENCE: Level III.

Accuracy of Predictive Algorithms in Total Hip and Knee Arthroplasty Acute Periprosthetic Joint Infections Treated With Debridement, Antibiotics, and Implant Retention (DAIR).

BACKGROUND: Debridement, antibiotics, and implant retention (DAIR) failure remains high for total hip and knee arthroplasty periprosthetic joint infection (PJI). We sought to determine the predictive value of the CRIME80 and KLIC for failure of DAIR in acute hematogenous (AH) and acute postoperative (AP) PJIs, respectively. METHODS: We identified 134 patients who underwent DAIR for AH PJI with <4 weeks of symptoms after index arthroplasty and 122 patients who underwent DAIR for AP PJI <90 days from index. In the AH group, 15 patients (11%) failed at 90 days and overall, 33 (25%) had failed by 2 years. In the AP group, 39 (32%) failed at 90 days and overall, 52 (43%) failed by 2 years. Logistic regression models were used to determine the area under the curve (AUC) to establish thresholds using the Youden index. RESULTS: For the AP cohort, AUCs were below 0.66 for KLIC, Charlson comorbidity index, Elixhauser comorbidity index, and McPherson host grade. For the AH cohort, 90-day AUCs were 0.70 for CRIME80 and below 0.66 for Charlson comorbidity index, Elixhauser comorbidity index, and McPherson host grade. In multivariate analysis controlling for age, sex, and body mass index, the CRIME80 AUC improved to 0.77 at 90 days. CONCLUSION: To the authors' knowledge, this study represents the first external validation of the KLIC and CRIME80 for predicting DAIR failure in a North American population. The results indicate that alternative methods for predicting DAIR failure at 90 days and 2 years for acute PJI are needed. LEVEL OF EVIDENCE: Prognostic III.

Utilization of Debridement, Antibiotics, and Implant Retention for Infection After Total Joint Arthroplasty Over a Decade in the United States.

BACKGROUND: Reported clinical outcomes have varied for debridement, antibiotics, and implant retention (DAIR) and little is known regarding trends in utilization. We sought to evaluate the rate of DAIR utilization for total knee arthroplasty (TKA) and total hip arthroplasty (THA) periprosthetic joint infection (PJI) over a decade and clinical factors associated with these trends. METHODS: A retrospective study of primary TKAs and THAs was performed using Medicare data from 2005 to 2014 using the PearlDiver database platform. Current Procedural Technology and International Classification of Diseases Ninth Edition codes identified patients who underwent a surgical revision for PJI, whether revision was a DAIR, as well as associated clinical factors including timing from index arthroplasty. RESULTS: The proportion of revision TKAs and THAs performed using DAIR was 27% and 12% across all years, respectively. This proportion varied by year for TKAs and THAs with a linear trend toward increasing relative use of DAIR estimated at 1.4% and 0.9% per year (P < .001; P < .001). DAIR for TKA and THA performed within 90 days increased at a faster rate, 3.4% and 2.1% per year (P < .001; P < .001). Trends over time in TKA DAIRs showed an association with Elixhauser Comorbidity Index (ECI), 0-5 group increasing at 2.0% per year (P = .03) and patients >85 years (P = .04). CONCLUSION: The proportion of revision arthroplasty cases for PJI managed with DAIR has been increasing over time in the United States, with the most substantial increase seen <90 days from index arthroplasty. Age, gender, and ECI had a minimal association with this trend, except in the TKA population >85 years and in those with a very low ECI score.

Treatment and Outcome of Periprosthetic Joint Infection in Unicompartmental Knee Arthroplasty.

BACKGROUND: Periprosthetic joint infection (PJI) after unicompartmental knee arthroplasty (UKA) is a devastating but poorly understood complication, with a paucity of published data regarding treatment and outcomes. This study analyzes the largest cohort of UKA PJIs to date comparing treatment outcome, septic and aseptic reoperation rates, and risk factors for treatment failure. METHODS: Twenty-one UKAs in 21 patients treated for PJI, as defined by Musculoskeletal Infection Society criteria, were retrospectively reviewed. Minimum and mean follow-up was 1 and 3.5 years, respectively. Fourteen (67%) patients had acute postoperative PJIs. Surgical treatment included 16 debridement, antibiotics, and implant retentions (DAIRs) (76%), 4 two-stage revisions (19%), and 1 one-stage revision (5%). Twenty (95%) PJIs were culture positive with Staphylococcus species identified in 15 cases (71%). RESULTS: Survivorship free from reoperation for infection at 1 year was 76% (95% confidence interval, 58%-93%). Overall survival from all-cause reoperation was 57% (95% confidence interval, 27%-87%) at 5 years. Two additional patients (10%) underwent aseptic revision total knee arthroplasty for lateral compartment degeneration 1 year after DAIR and tibial aseptic loosening 2.5 years after 2-stage revision. All patients who initially failed PJI UKA treatment presented with acute postoperative PJIs (5 of 14; 36%). CONCLUSION: Survivorship free from persistent PJI at 1 year is low at 76% but is consistent with similar reports of DAIRs for total knee arthroplasties. Furthermore, there is low survivorship free from all-cause reoperation of 71% and 57% at 2 and 5 years, respectively. Surgeons should be aware of these poorer outcomes and consider treating UKA PJI early and aggressively.

Opioid prescription trends after ambulatory anterior cervical discectomy and fusion.

BACKGROUND CONTEXT: Opioid utilization has been well studied for inpatient anterior cervical discectomy and fusion (ACDF). However, the amount and type of opioids prescribed following ambulatory ACDF and the associated risk of persistent use are largely unknown. PURPOSE: To characterize opioid prescription filling following single-level ambulatory ACDF compared with inpatient procedures. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Opioid-naive patients who underwent ambulatory (no overnight stay) or inpatient single-level ACDF from 2011 to 2019 were identified from a national insurance database. OUTCOME MEASURES: Rate, amount, and type of perioperative opioid prescription. METHODS: Opioid-naive patients who underwent ambulatory (no overnight stay) or inpatient single-level ACDF from 2011 to 2019 were identified from a national insurance database. Perioperative opioids were defined as opioid prescriptions 30 days before and 14 days after the procedure. Rate, amount, and type of opioid prescription were characterized. Multivariable analyses controlling for any differences in demographics and comorbidities between the two treatment groups were utilized to determine any association between surgical setting and persistent opioid use (defined as the patient still filling new opioid prescriptions >90 days postoperatively). RESULTS: A total of 42,521 opioid-naive patients were identified, of which 2,850 were ambulatory and 39,671 were inpatient. Ambulatory ACDF was associated with slightly increased perioperative opioid prescription filling (52.7% vs 47.3% for inpatient procedures; p<.001). Among the 20,280 patients (47.7%) who filled perioperative opioid prescriptions, the average amount of opioids prescribed (in morphine milligram equivalents) was similar between ambulatory and inpatient procedures (550 vs 540, p=.413). There was no association between surgical setting and persistent opioid use in patients who filled a perioperative opioid prescription, even after controlling for comorbidities, (adjusted odds ratio, 1.15, p=.066). CONCLUSIONS: Ambulatory ACDF patients who filled perioperative opioid prescriptions were prescribed a similar amount of opioids as those undergoing inpatient procedures. Further, ambulatory ACDF does not appear to be a risk factor for persistent opioid use. These findings are important for patient counseling as well as support the safety profile of this new surgical pathway.

Clinical and Histological Features of Prosthetic Joint Infections May Differ in Patients With Inflammatory Arthritis and Osteoarthritis.

Background: Patients with inflammatory arthritis are at increased risk of prosthetic joint infections (PJIs), but diagnosis in these patients can be challenging because active inflammatory arthritis produces elevated inflammatory markers that may mimic those seen in PJI. Purpose: In this pilot study, we sought to identify the clinical, microbiologic, and histopathologic features of culture-positive and culture-negative PJI in patients with inflammatory arthritis who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA). We also sought to obtain preliminary data to support a definitive study of optimal methods for PJI diagnosis in patients with inflammatory arthritis. Methods: We performed a retrospective analysis of TKA and THA patients treated for PJI from 2009 to 2018 at a single tertiary care orthopedic institution. Data were extracted from a longitudinally maintained hospital infection database. We reviewed hematoxylin and eosin slides of osteoarthritis and inflammatory arthritis PJI cases matched 3:1, respectively, by age, sex, and culture status. Clinical characteristics were evaluated using the Fisher exact test, χ2 test, Student t test, and Mann-Whitney U test where appropriate. Results: A total of 807 PJI cases were identified (36 inflammatory arthritis and 771 osteoarthritis cases). Patients with inflammatory arthritis presented younger, had a higher Charlson Comorbidity Index, more frequently used glucocorticoids, were more likely women, and had a higher proportion of culture-negative PJI compared with osteoarthritis patients. Of the 88 inflammatory arthritis cases reviewed for histopathology, a higher proportion of culture-positive than culture-negative PJI cases had >10 polymorphonuclear leucocytes per high-power field and met Musculoskeletal Infection Society criteria but presented with less chronic inflammation. Conclusions: This retrospective prognostic study suggests that culture-negative PJI may be more frequent in patients with inflammatory arthritis than in those with osteoarthritis. Chronic infections, antibiotic use, or misdiagnosis may be contributing factors to unclear PJI diagnoses among culture-negative cases. This preliminary work supports the need for further studies to assess the differences in clinical features between culture-negative and culture-positive PJI in patients with inflammatory arthritis and the ability of biological diagnostic markers to discriminate between them in this population.

History of COVID-19 Was Not Associated With Length of Stay or In-Hospital Complications After Elective Lower Extremity Joint Replacement.

BACKGROUND: The impact of previous SARS-CoV-2 infection on the morbidity of elective total joint arthroplasty (TJA) is not fully understood. This study reports on the association between previous COVID-19 disease, hospital length of stay (LOS), and in-hospital complications after elective primary TJA. METHODS: Demographics, comorbidities, LOS, and in-hospital complications of consecutive 340 patients with a history of COVID-19 were compared with those of 5014 patients without a history of COVID-19 undergoing TJA. History of COVID-19 was defined as a positive IgG antibody test for SARS-CoV-2 before surgery. All patients were given both antibody and polymerase chain reaction tests before surgery. RESULTS: Patients with a history of COVID-19 were more likely to be obese (43.8% vs 32.4%, P < .001), Black (15.6% vs 6.8%, P < .001), or Hispanic (8.5% vs 5.4%, P = .028) than patients without a history of COVID-19. COVID-19 treatment was reported by 6.8% of patients with a history of COVID-19. Patients with a history of COVID-19 did not have a significantly longer median LOS after controlling for other factors (for hip replacements, median 2.9 h longer, 95% confidence interval = -2.0 to 7.8, P = .240; for knee replacements, median 4.1 h longer, 95% confidence interval = -2.4 to 10.5, P = .214), but a higher percentage were discharged to a post-acute care facility (4.7% vs 1.9%, P = .001). There was no significant difference in in-hospital complication rates between the 2 groups (0/340 = 0.0% vs 22/5014 = 0.44%, P = .221). CONCLUSIONS: We do not find differences in LOS or in-hospital complications between the 2 groups. However, more work is needed to confirm these findings, particularly for patients with a history of more severe COVID-19. LEVEL OF EVIDENCE: II.

Factors Associated With an Intra-articular Infection After Anterior Cruciate Ligament Reconstruction: A Large Single-Institution Cohort Study.

BACKGROUND: An intra-articular infection after anterior cruciate ligament (ACL) reconstruction (ACLR) is a rare complication but one with potentially devastating consequences. The rare nature of this complication raises difficulties in detecting risk factors associated with it and with worse outcomes after one has occurred. PURPOSE: To (1) evaluate the association between an infection after ACLR and potential risk factors in a large single-center cohort of patients who had undergone ACLR and (2) assess the factors associated with ACL graft retention versus removal. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: All ACLR procedures performed at our institution between January 2010 and December 2018 were reviewed; a total of 11,451 procedures were identified. A retrospective medical record review was performed to determine the incidence of infections, patient and procedure characteristics associated with an infection, infection characteristics, incidence of ACL graft retention, and factors associated with the retention versus removal of an ACL graft. Multivariable logistic regression analysis was used to identify potential risk factors for an infection after ACLR. RESULTS: Of the 11,451 ACLR procedures, 48 infections were identified (0.42%). Multivariable logistic regression analysis revealed revision ACLR (odds ratio [OR], 3.13 [95% CI, 1.55-6.32]; P = .001) and younger age (OR, 1.06 [95% CI, 1.02-1.10]; P = .001) as risk factors for an infection. Compared with bone-patellar tendon-bone autografts, both hamstring tendon autografts (OR, 4.39 [95% CI, 2.15-8.96]; P < .001) and allografts (OR, 5.27 [95% CI, 1.81-15.35]; P = .002) were independently associated with an increased risk of infections. Overall, 15 ACL grafts were removed (31.3%). No statistically significant differences besides the number of irrigation and debridement procedures were found for retained versus removed grafts, although some trends were identified (P = .054). CONCLUSION: In a large single-center cohort of patients who had undergone ACLR and those with an infection after ACLR, patients with revision cases and younger patients were found to have a higher incidence of infection. The use of bone-patellar tendon-bone autografts was found to be associated with the lowest risk of infection after ACLR compared with both hamstring tendon autografts and allografts. Larger cohorts with a larger number of infection cases are needed to determine the factors associated with graft retention versus removal.

Trends of Utilization and 90-Day Complication Rates for Computer-Assisted Navigation and Robotic Assistance for Total Knee Arthroplasty in the United States From 2010 to 2018.

BACKGROUND: Computer-assisted navigation (CAN) and robotic assistance (RA) for total knee arthroplasty (TKA) are gaining in popularity. The purpose of this study is to update the literature on United States technology-assisted TKA trends of national utilization, regional utilization, and 90-day complication rates requiring readmission. METHODS: Patients who underwent primary, elective TKA between 2010 and 2018 were retrospectively identified in the PearlDiver All Payer Claims Database (PearlDiver Technologies Inc.). TKAs were classified as conventional, CAN, or RA based on International Classification of Diseases nineth or tenth revision and Current Procedural Technology codes. Annual rates and regional trends of each type of TKA were reported. Ninety-day complications requiring readmission for each group were captured. Multivariable logistic regression was used to identify odds ratios (OR) for all-cause readmission based on TKA modality. RESULTS: Of the 1,307,411 elective TKAs performed from 2010 to 2018, 92.8% were conventional, and 7.7% were technology-assisted (95.2% CAN and 4.9% RA). RA-TKA had the greatest increase in utilization (+2204%). The Western region had the highest utilization of technologies for TKA, while the Midwestern region had the lowest. Ninety-day postoperative complications requiring readmission were highest for conventional TKA and lowest for RA-TKA. RA-TKA (OR 0.68; 97.5% confidence interval 0.56-0.83, P < .001) and CAN-TKA (OR 0.93; 97.5% confidence interval 0.88-0.97, P < .05) had significantly lower odds of all-cause 90-day complications requiring readmission than conventional TKA. CONCLUSION: Utilization of RA-TKA and CAN-TKA continues to rise across the United States. The use of these technologies is associated with a lower OR of readmission within 90 days postoperatively.

Periprosthetic joint infection after primary TKA in the medicare population: How frequently are patients revised at a different hospital?

BACKGROUND: Periprosthetic infection (PJI) after total knee arthroplasty (TKA) places a significant burden on hospitals. We sought to describe the proportion of patients undergoing revision for PJI at a different hospital within one year of primary TKA and whether patient characteristics or hospital volume were associated with this change. METHODS: Medicare data from 2005 to 2014 was retrospectively reviewed using PearlDiver. All patients over 64 years undergoing revision for PJI within one year of primary TKA were stratified by the revision occurring within 90 days. Hospitals were grouped by annual TKA volume as Low (<50), Medium (51-100), High (101-200), and Very High (>200). Associations of patient characteristics and hospital volume with revision at a different hospital were assessed using Chi-squared tests and Somers' D. RESULTS: Of 8,337 patients undergoing revision within 90 days of TKA, 1,370 (16%) were revised at a different hospital. Changing hospitals was associated with having primary TKA at a lower volume hospital (24% for low, 15% medium, 12% high, and 12% very high; P < 0.001). Of 7,608 patients undergoing revision between 91 and 365 days, 1,110 (15%) were revised at a different hospital. Changing hospitals was associated with having primary TKA at a lower volume hospital (26% for low, 14% medium, 10% high, and 9% very high; P < 0.001). Changing hospitals was not associated with sex or age. CONCLUSION: Patients frequently undergo revision for PJI at a different hospital, even within 90 days of TKA. Further research is needed to understand these implications of this care pathway shift.

Assessing the Role of Daptomycin as Antibiotic Therapy for Staphylococcal Prosthetic Joint Infection.

Background: The role of daptomycin, a potent, safe, convenient anti-staphylococcal antibiotic, in treatment of prosthetic joint infection (PJI) is unclear. We evaluated our experience with the largest cohort of patients with staphylococcal PJI managed with daptomycin. Methods: A cohort of staphylococcal hip and knee PJI treated with daptomycin was identified by hospital records from 2009 to 2016. All cases met Musculoskeletal Infection Society International Consensus criteria for PJI. The primary endpoint was 2 year prosthesis retention. Univariate analyses and regression statistics were calculated. Results: 341 patients with staphylococcal PJI were analyzed. 154 two-stages (77%) and 74 DAIR procedures (52%) met criteria for treatment success at 2 years. 77 patients were treated with daptomycin, of which 34 two-stages (68%) and 15 DAIRs (56%) achieved treatment success. Pairwise and regression analysis found no association between treatment success and daptomycin use. Organism (DAIR only) and Charlson Comorbidity Index scores (DAIR and two-stage) were significantly associated with treatment outcome. Six daptomycin patients (7.8%) had adverse side effects. Discussion: Daptomycin fared no better or worse than comparable antibiotics in a retrospective cohort of staphylococcal hip and knee PJI patients, regardless of surgical strategy. Conclusion: The convenient dosing, safety, and potency of daptomycin make it an attractive antibiotic for staphylococcal PJI. However, these advantages must be weighed against higher costs and rare, but serious side effects.

Clinical Experience with COVID-19 at a Specialty Orthopedic Hospital Converted to a Pandemic Overflow Field Hospital.

BACKGROUND: COVID-19, the illness caused by the novel coronavirus, SARS-CoV-2, has sickened millions and killed hundreds of thousands as of June 2020. New York City was affected gravely. Our hospital, a specialty orthopedic hospital unaccustomed to large volumes of patients with life-threatening respiratory infections, underwent rapid adaptation to care for COVID-19 patients in response to emergency surge conditions at neighboring hospitals. PURPOSES: We sought to determine the attributes, pharmacologic and other treatments, and clinical course in the cohort of patients with COVID-19 who were admitted to our hospital at the height of the pandemic in April 2020 in New York City. METHODS: We conducted a retrospective observational cohort study of all patients admitted between April 1 and April 21, 2020, who had a diagnosis of COVID-19. Data were gathered from the electronic health record and by manual chart abstraction. RESULTS: Of the 148 patients admitted with COVID-19 (mean age, 62 years), ten patients died. There were no deaths among non-critically ill patients transferred from other hospitals, while 26% of those with critical illness died. A subset of COVID-19 patients was admitted for orthopedic and medical conditions other than COVID-19, and some of these patients required intensive care and ventilatory support. CONCLUSION: Professional and organizational flexibility during pandemic conditions allowed a specialty orthopedic hospital to provide excellent care in a global public health emergency.

Two Cys residues essential for von Willebrand factor multimer assembly in the Golgi.

Von Willebrand factor (VWF) dimerizes through C-terminal CK domains, and VWF dimers assemble into multimers in the Golgi by forming intersubunit disulfide bonds between D3 domains. This unusual oxidoreductase reaction requires the VWF propeptide (domains D1D2), which acts as an endogenous pH-dependent chaperone. The cysteines involved in multimer assembly were characterized by using a VWF construct that encodes the N-terminal D1D2D'D3 domains. Modification with thiol-specific reagents demonstrated that secreted D'D3 monomer contained reduced Cys, whereas D'D3 dimer and propeptide did not. Reduced Cys in the D'D3 monomer were alkylated with N-ethylmaleimide and analyzed by mass spectrometry. All 52 Cys within the D'D3 region were observed, and only Cys(1099) and Cys(1142) were modified by N-ethylmaleimide. When introduced into the D1D2D'D3 construct, the mutation C1099A or C1142A markedly impaired the formation of D'D3 dimers, and the double mutation prevented dimerization. In full-length VWF, the mutations C1099A and C1099A/C1142A prevented multimer assembly; the mutation C1142A allowed the formation of almost exclusively dimers, with few tetramers and no multimers larger than hexamers. Therefore, Cys(1099) and Cys(1142) are essential for the oxidoreductase mechanism of VWF multimerization. Cys(1142) is reported to form a Cys(1142)-Cys(1142) intersubunit bond, suggesting that Cys(1099) also participates in a Cys(1099)-Cys(1099) disulfide bond between D3 domains. This arrangement of intersubunit disulfide bonds implies that the dimeric N-terminal D'D3 domains of VWF subunits align in a parallel orientation within VWF multimers.