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803


Minimally and Non-invasive Approaches to Rejection Identification in Vascularized Composite Allotransplantation

Stead, Thor S; Brydges, Hilliard T; Laspro, Matteo; Onuh, Ogechukwu C; Chaya, Bachar F; Rabbani, Piul S; Lu, Catherine P; Ceradini, Daniel J; Gelb, Bruce E; Rodriguez, Eduardo D
OBJECTIVE:Rejection is common and pernicious following Vascularized Composite Allotransplantation (VCA). Current monitoring and diagnostic modalities include the clinical exam which is subjective and biopsy with dermatohistopathologic Banff grading, which is subjective and invasive. We reviewed literature exploring non- and minimally invasive modalities for diagnosing and monitoring rejection (NIMMs) in VCA. METHODS:PubMed, Cochrane, and Embase databases were queried, 3125 unique articles were reviewed, yielding 26 included studies exploring 17 distinct NIMMs. Broadly, NIMMs involved Imaging, Liquid Biomarkers, Epidermal Sampling, Clinical Grading Scales, and Introduction of Additional Donor Tissue. RESULTS:Serum biomarkers including MMP3 and donor-derived microparticles rose with rejection onset. Epidermal sampling non-invasively enabled measurement of cytokine & gene expression profiles implicated in rejection. Both hold promise for monitoring. Clinical grading scales were useful diagnostically as was reflection confocal microscopy. Introducing additional donor tissue showed promise for preemptively identifying rejection but requires additional allograft tissue burden for the recipient. CONCLUSION/CONCLUSIONS:NIMMs have the potential to dramatically improve monitoring and diagnosis in VCA. Many modalities show promise however, additional research is needed and a multimodal algorithmic approach should be explored.
PMID: 37625211
ISSN: 1557-9816
CID: 5599092

Reversible Differentiation of Melanocyte Stem Cells: Designed to Last or Be Lost?

Sun, Qi; Brinks, Anna; Ito, Mayumi
PMID: 37676220
ISSN: 1523-1747
CID: 5607832

Home discharge location is safest following fracture of the hip

Deemer, Alexa R; Ganta, Abhishek; Leucht, Philipp; Konda, Sanjit; Tejwani, Nirmal C; Egol, Kenneth A
PURPOSE/OBJECTIVE:To determine the factors associated with discharge location in patients with hip fractures and whether home discharge was associated with a lower readmission and complication rate. METHODS:Hip fracture patients who presented to our academic medical center for operative management of a hip fracture were enrolled into an IRB-approved hip fracture database. Radiographs, demographics, and injury details were recorded at the time of presentation. Patients were grouped based upon discharge disposition: home (with or without home services), acute rehabilitation facility (ARF), or sub-acute rehabilitation facility (SAR). RESULTS:The cohorts differed in marital status, with a greater proportion of patients discharged to home being married (51.7% vs. 43.8% vs. 34.1%) (P < 0.05). Patients discharged to home were less likely to require an assistive device (P < 0.05). Patients discharged to home experienced fewer post-operative complications (P < 0.05) and had lower readmission rates (P < 0.05). Being married was associated with an increased likelihood of discharge to home (OR = 1.679, CI = 1.391-2.028, P < 0.001). Being enrolled in Medicare/Medicaid was associated with decreased odds of discharge to home (OR = 0.563, CI = 0.457-0.693, P < 0.001). Use of an assistive device was associated with decreased odds of discharge to home (OR = 0.398, CI = 0.326-0.468, P < 0.001). Increases in CCI (OR = 0.903, CI = 0.846-0.964, P = 0.002) and number of inpatient complications (OR = 0.708, CI = 0.532-0.943, P = 0.018) were associated with decreased odds of home discharge. CONCLUSION/CONCLUSIONS:Hip fracture patients discharged to home were healthier and more functional at baseline, and also less likely to have had a complicated hospital course. Those discharged to home also had lower rates of readmission and post-operative complications. LEVEL OF EVIDENCE/METHODS:III.
PMID: 37219687
ISSN: 1432-1068
CID: 5508332

One year later: How outcomes of hip fractures treated during the "first wave" of the COVID-19 pandemic were affected

Konda, Sanjit R; Esper, Garrett W; Meltzer-Bruhn, Ariana T; Solasz, Sara J; Ganta, Abhishek; Leucht, Philipp; Tejwani, Nirmal C; Egol, Kenneth A
The purpose of this study was to assess the impact of COVID-19 on long-term outcomes in the geriatric hip fracture population. We hypothesize that COVID + geriatric hip fracture patients had worse outcomes at 1-year follow-up. Between February and June 2020, 224 patients > 55 years old treated for a hip fracture were analyzed for demographics, COVID status on admission, hospital quality measures, 30- and 90-day readmission rates, 1-year functional outcomes (as measured by the EuroQol- 5 Dimension [EQ5D-3L] questionnaire), and inpatient, 30-day, and 1-year mortality rates with time to death. Comparative analyses were conducted between COVID + and COVID- patients. Twenty-four patients (11%) were COVID + on admission. No demographic differences were seen between cohorts. COVID + patients experienced a longer length of stay (8.58 ± 6.51 vs. 5.33 ± 3.09, p < 0.01) and higher rates of inpatient (20.83% vs. 1.00%, p < 0.01), 30-day (25.00% vs. 5.00%, p < 0.01), and 1-year mortality (58.33% vs. 18.50%, p < 0.01). There were no differences seen in 30- or 90-day readmission rates, or 1-year functional outcomes. While not significant, COVID + patients had a shorter average time to death post-hospital discharge (56.14 ± 54.31 vs 100.68 ± 62.12, p = 0.171). Pre-vaccine, COVID + geriatric hip fracture patients experienced significantly higher rates of mortality within 1 year post-hospital discharge. However, COVID + patients who did not die experienced a similar return of function by 1-year as the COVID- cohort.
PMCID:10075150
PMID: 37020155
ISSN: 2035-5114
CID: 5613302

Combined Face and Whole Eye Transplantation: Cadaveric Rehearsals and Feasibility Assessment

Brydges, Hilliard T.; Onuh, Ogechukwu C.; Chaya, Bachar F.; Tran, David L.; Cassidy, Michael F.; Dedania, Vaidehi S.; Ceradini, Daniel J.; Rodriguez, Eduardo D.
Background: In properly selected patients, combined face and whole eye transplantation (FWET) may offer a more optimal aesthetic and potentially functional outcome while avoiding the complications and stigma of enucleation and prosthetics. This study presents the most comprehensive cadaveric assessment for FWET to date, including rehearsal allograft procurement on a brain-dead donor. Methods: Over a 2-year period, 15 rehearsal dissections were performed on 21 cadavers and one brain-dead donor. After identification of a potential recipient, rehearsals assessed clinical feasibility and enabled operative planning, technical practice, refinement of personalized equipment, and improved communication among team members. Operative techniques are described. Results: Facial allograft procurement closely followed previously described face transplant techniques. Ophthalmic to superficial temporal (O-ST) vessel anastomosis for globe survival was assessed. Craniectomy allowed for maximal optic nerve and ophthalmic vessel pedicle length. Appropriate pedicle length and vessel caliber for O-ST anastomosis was seen. Research procurement demonstrated collateral blood flow to the orbit and surrounding structures from the external carotid system as well as confirmed the feasibility of timely O-ST anastomosis. Personalized cutting guides enabled highly accurate bony inset. Conclusions: This study formalizes an approach to FWET, which is feasible for clinical translation in judiciously selected patients. O-ST anastomosis seems to minimize retinal ischemia time and allow perfusion of the combined allograft on a single external carotid pedicle. Although restoration of vision likely remains out of reach, globe survival is possible.
SCOPUS:85178043696
ISSN: 2169-7574
CID: 5621122

Effect of concomitant deformity correction on patient outcomes following femoral (OTA type 32) nonunion repair

Adams, Jack C; Konda, Sanjit R; Ganta, Abhishek; Leucht, Philipp; Egol, Kenneth A
INTRODUCTION/BACKGROUND:The purpose of this study was to determine what effect, if any, concomitant deformity correction has on outcomes following femoral nonunion repair. METHODS:605 consecutive patients who presented to our center with a long bone nonunion treated by one of 3 surgeons was queried. Sixty-two patients (10 %) with complete follow up were treated for a fracture nonunion following a Type 32 femur fracture (subtrochanteric, femoral shaft or distal third metaphysis) over an 11-year period. Twenty of these patients underwent a deformity correction (DC)-angular, rotational, or a combination of both-as part of their femoral reconstruction. Patient demographics and initial injury information was reviewed and compared. Outcomes including radiographic healing, time to union, postoperative complications, patient reported pain scores, and functional outcome scores using the Short Musculoskeletal Functional Assessment (SMFA) were recorded. Patients with and without deformity correction were analyzed and compared using independent T-tests and Chi-Square tests. RESULTS:Compared to the non-deformity correction (NDC) cohort, the DC cohort demonstrated a worse complication profile. Notably, the DC cohort had longer time to union (11.6 ± 7.3 months vs 7.6 ± 8.5 months, P = 0.042), reported significantly higher VAS pain scores at 1-year post-op (4.2 ± 2.8 vs 2.3 ± 2.6, P = 0.007), experienced more complications (25 % vs 4.8 %, P = 0.019), and had a higher rate of secondary procedures (30 % vs 4.8 %, P = 0.006). The DC patients reported less improvement in functional capability as displayed by a smaller average improvement in initial and final SMFA scores (P = 0.042) There was no difference in ultimate bone healing (P = 0.585), baseline SMFA (P = 0.294), and latest SMFA (P = 0.066). CONCLUSION/CONCLUSIONS:Deformity correction, if needed as part of femoral nonunion repair, is associated with an increased time to heal, greater rate of complications and diminished improvement of functionality. Eventual healing and patient reported outcomes were similar whether a deformity correction is necessary or not. LEVEL OF EVIDENCE/METHODS:III.
PMID: 37992462
ISSN: 1879-0267
CID: 5608682

Epidemiology of distal radius fractures: Elucidating mechanisms, comorbidities, and fracture classification using the national trauma data bank

Chinta, Sachin R; Cassidy, Michael F; Tran, David L; Brydges, Hilliard T; Ceradini, Daniel J; Bass, Jonathan L; Agrawal, Nikhil A
BACKGROUND:An update on the epidemiology of distal radius fractures in the United States is necessary, particularly as the elderly population grows. Additionally, age and frailty have been associated with complications following surgical fixation of DRFs. Herein, we utilize the National Trauma Data Bank, a robust nationwide resource, to investigate the relationship between demographics, comorbidities, injury and fracture characteristics, and admission details. METHODS:Patients with isolated distal radius fractures were identified from the National Trauma Data Bank (2016-2019) according to ICD-10 codes. Univariate and multivariate regressions were conducted to determine independent risk factors for bilateral fractures, displaced fractures, open fractures, as well as length of hospital stay and adverse discharge disposition for patients undergoing inpatient surgical fixation. RESULTS:The incidence of DRFs was 3.6/1,000 trauma-related emergency department visits and 10.8/1,000 upper extremity traumas. Trauma mechanism was significantly associated with displaced and open fractures. Age (OR 1.01, 95% CI 1.01-1.01), BMI (OR 1.02, 95% CI 1.01-1.02), smoking (OR 1.34, 95% CI 1.15-1.57), and alcohol level (trace: OR 2.18, 95% CI 1.41-3.29; intoxicated: OR 2.20, 95% CI 1.63-2.95) were significantly associated with open fractures. Machinery (β=2.04, 95% CI 1.00-3.08) and MVT (β=0.39, 95% CI 0.08-0.69) mechanisms were independent risk factors for longer length of stay. mFI-5 was an independent risk factor, in a stepwise fashion, for both length of stay and adverse discharge disposition. CONCLUSIONS:High-energy mechanisms and risk factors for poor skin quality were significantly associated with open fractures. mFI-5 was an independent risk factor for longer length of stay and non-routine discharges in patients of all ages, despite controlling for other comorbidities, unrelated complications, and mechanism of injury. Trauma mechanism was an independent risk factor for prolonged length of stay only, particularly in patients younger than 65 years of age.
PMID: 38029683
ISSN: 1879-0267
CID: 5590952

Combined Face and Whole Eye Transplantation: Cadaveric Rehearsals and Feasibility Assessment

Brydges, Hilliard T; Onuh, Ogechukwu C; Chaya, Bachar F; Tran, David L; Cassidy, Michael F; Dedania, Vaidehi S; Ceradini, Daniel J; Rodriguez, Eduardo D
BACKGROUND/UNASSIGNED:In properly selected patients, combined face and whole eye transplantation (FWET) may offer a more optimal aesthetic and potentially functional outcome while avoiding the complications and stigma of enucleation and prosthetics. This study presents the most comprehensive cadaveric assessment for FWET to date, including rehearsal allograft procurement on a brain-dead donor. METHODS/UNASSIGNED:Over a 2-year period, 15 rehearsal dissections were performed on 21 cadavers and one brain-dead donor. After identification of a potential recipient, rehearsals assessed clinical feasibility and enabled operative planning, technical practice, refinement of personalized equipment, and improved communication among team members. Operative techniques are described. RESULTS/UNASSIGNED:Facial allograft procurement closely followed previously described face transplant techniques. Ophthalmic to superficial temporal (O-ST) vessel anastomosis for globe survival was assessed. Craniectomy allowed for maximal optic nerve and ophthalmic vessel pedicle length. Appropriate pedicle length and vessel caliber for O-ST anastomosis was seen. Research procurement demonstrated collateral blood flow to the orbit and surrounding structures from the external carotid system as well as confirmed the feasibility of timely O-ST anastomosis. Personalized cutting guides enabled highly accurate bony inset. CONCLUSIONS/UNASSIGNED:This study formalizes an approach to FWET, which is feasible for clinical translation in judiciously selected patients. O-ST anastomosis seems to minimize retinal ischemia time and allow perfusion of the combined allograft on a single external carotid pedicle. Although restoration of vision likely remains out of reach, globe survival is possible.
PMCID:10653600
PMID: 38025647
ISSN: 2169-7574
CID: 5617242

Osteogenic differentiation and reconstruction of mandible defects using a novel resorbable membrane: An in vitro and in vivo experimental study

Bergamo, Edmara T P; Balderrama, Ísis de Fátima; Ferreira, Marcel Rodrigues; Spielman, Robert; Slavin, Blaire V; Torroni, Andrea; Tovar, Nick; Nayak, Vasudev V; Slavin, Benjamin R; Coelho, Paulo G; Witek, Lukasz
To evaluate the cellular response of both an intact fish skin membrane and a porcine-derived collagen membrane and investigate the bone healing response of these membranes using a translational, preclinical, guided-bone regeneration (GBR) canine model. Two different naturally sourced membranes were evaluated in this study: (i) an intact fish skin membrane (Kerecis Oral®, Kerecis) and (ii) a porcine derived collagen (Mucograft®, Geistlich) membrane, positive control. For the in vitro experiments, human osteoprogenitor (hOP) cells were used to assess the cellular viability and proliferation at 24, 48, 72, and 168 h. ALPL, COL1A1, BMP2, and RUNX2 expression levels were analyzed by real-time PCR at 7 and 14 days. The preclinical component was designed to mimic a GBR model in canines (n = 12). The first step was the extraction of premolars (P1-P4) and the 1st molars bilaterally, thereby creating four three-wall box type defects per mandible (two per side). Each defect site was filled with bone grafting material, which was then covered with one of the two membranes (Kerecis Oral® or Mucograft®). The groups were nested within the mandibles of each subject and membranes randomly allocated among the defects to minimize potential site bias. Samples were harvested at 30-, 60-, and 90-days and subjected to computerized microtomography (μCT) for three-dimensional reconstruction to quantify bone formation and graft degradation, in addition to histological processing to qualitatively analyze bone regeneration. Neither the intact fish skin membrane nor porcine-based collagen membrane presented cytotoxic effects. An increase in cell proliferation rate was observed for both membranes, with the Kerecis Oral® outperforming the Mucograft® at the 48- and 168-hour time points. Kerecis Oral® yielded higher ALPL expression relative to Mucograft® at both 7- and 14-day points. Additionally, higher COL1A1 expression was observed for the Kerecis Oral® membrane after 7 days but no differences were detected at 14 days. The membranes yielded similar BMP2 and RUNX2 expression at 7 and 14 days. Volumetric reconstructions and histologic micrographs indicated gradual bone ingrowth along with the presence of particulate bone grafts bridging the defect walls for both Kerecis Oral® and Mucograft® membranes, which allowed for the reestablishment of the mandible shape after 90 days. New bone formation significantly increased from 30 to 60 days, and from 60 to 90 days in vivo, without significant differences between membranes. The amount of bovine grafting material (%) within the defects significantly decreased from 30 to 90 days. Collagen membranes led to an upregulation of cellular proliferation and adhesion along with increased expression of genes associated with bone healing, particularly the intact fish skin membrane. Despite an increase in the bone formation rate in the defect over time, there was no significant difference between the membranes.
PMID: 37470190
ISSN: 1552-4981
CID: 5535932

In vitro assessment of the effect of luting agents, abutment height, and fatigue on the retention of zirconia crowns luted to titanium base implant abutments

Strazzi-Sahyon, Henrico B; Bergamo, Edmara T P; Gierthmuehlen, Petra C; Lopes, Adolfo C O; Alves, Larissa M M; Benalcázar Jalkh, Ernesto B; Zahoui, Abbas; Coelho, Paulo G; de Carvalho, Alexandre M; Bonfante, Estevam A
STATEMENT OF PROBLEM/BACKGROUND:The bonding of implant-supported prostheses is determined by abutment material, convergence angle, height, surface treatment, and luting agents. However, studies evaluating the bonding of luting agents to titanium base abutments with different heights under fatigue conditions are scarce. PURPOSE/OBJECTIVE:The purpose of this in vitro study was to evaluate the retention of zirconia crowns bonded with different luting agents to titanium base abutments of different heights before and after fatigue testing. MATERIAL AND METHODS/METHODS:cycles; 100 N; and 15 Hz), followed by pull-out testing of fatigued specimens. Collected data were statistically evaluated by using a linear mixed model after post hoc comparisons by the least significant difference test (α=.05). RESULTS:Luting agents, abutment heights, and fatigue influenced the bonding retention of zirconia crowns to titanium base abutments. SU/RU agents promoted higher pull-out compared with MP/GC for both abutment heights before and after fatigue. Higher abutment height increased pull-out regarding lower abutment height for SU/RU materials before and after fatigue testing. Although fatigue had no significant effect on the pull-out of MP/GC, lower bond retention was observed for SU/RU after fatigue, regardless of abutment height. CONCLUSIONS:Luting agent composition and the interaction with abutment height and fatigue influenced the retention of zirconia crowns to titanium base abutments.
PMID: 37684141
ISSN: 1097-6841
CID: 5610182