Single Digit Index Finger Amputation—To Replant or Not? Amputation Isolee de L’index — Reimplanter ou Pas?
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ABSTRACT:
SUBMITTER: Thibedeau M
PROVIDER: S-EPMC9900044 | biostudies-literature | 2021 Aug
REPOSITORIES: biostudies-literature
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Project description:Here we present single-cell RNA sequencing (scRNA-seq) data of untreated digit amputation wound cells that can be induced by BMP9 to undergo chondrogenesis to determine the responsive cell type
2021-12-31 | GSE185197 | GEO
Project description:Purpose: Repair of distal phalanx amputation is widely studied and thought to occur through a regenerative process. Single-cell RNA sequencing (scRNA) has greatly improved the ability to characterize the cells that are involved in regeneration and abnormal healing of bone and soft tissue. Given the disorganized architecture of digit tip “regenerated” bone and its common progenitor cell to the pathologic process of heterotopic ossification, we hypothesized that digit tip repair after injury follows a program of aberrant wound repair rather than true regeneration of normal bone tissue. Methods: ScRNA data of mouse digit tip amputation (DTA) and embryonic limb development (EMB) was downloaded from NBCI GEO data base ascension number GSE135985. Additionally, scRNA data from heterotopic ossification (HO) was downloaded from GSE126060. HO, DTA, and EMB datasets were clustered individually. HO was merged and aligned with EMB and DT in separate analyses. Cells expressing the mesenchymal progenitor cell (MPC) marker Pdgfra, which we have shown to differentiate into HO and others have shown to differentiate into bone after DTA, were identified and analyzed in the HO-DTA and HO-EMB datasets. Monocle 2, Seurat 3.1.1, and Pearson correlation analysis were used for analysis and visualization. Immunostaining for markers present in DTA (ACAN, FBN-2, LTBP2) was performed on sections collected from a murine model of traumatic HO in Pdgfra-CreER;TdTomato mice induced with tamoxifen one-week prior to HO-forming injury. Results: MPC clusters from DTA and HO and from EMB and HO were aligned and projected using UMAP to compare transcription profiles. Across the timepoints, MPCs in the DTA and HO occupy similar regions of the UMAP plot, while MPCs in EMB and HO occupy largely independent regions, with only overlap at the latest time points. Using Monocle 2, cells were placed on a virtual timeline based on similarities in transcription. MPCs from DTA and HO meet at the same location on the trajectory following injury. In the EMB to HO comparison, cells only occupy similar regions of the trajectory at post-natal day 3 suggesting that bone is formed by different pathways. To understand correlations between time points, transcriptomes were also compared by Pearson analysis. MPCs following HO and DTA injuries occupy similar regions of the plot while MPCs in EMB and HO only occupy similar regions of the correlation plot at P3. Markers previously identified to be upregulated in MPCs in DTA were also upregulated in MPCs in HO by both scRNA and immunofluorescent histology. Conclusions: Cells responsible for bone repair following DTA show similar transcriptional profiles as MPCs in traumatic HO and dissimilar to MPCs in EMB. Furthermore, MPCs in both digit tip repair and HO follow trajectories that do not overlap with embryonic limb development. Thus, we demonstrate for the first time, that the process following DTA is not truly regeneration and follows programs of aberrant repair as seen in HO.
| S-EPMC8312837 | biostudies-literature
Project description:A major goal of regenerative medicine is to stimulate tissue regeneration after traumatic injury. We previously discovered that treating digit amputation wounds with BMP2 in neonatal mice stimulates endochondral ossification to regenerate the stump bone. Here we show that treating the amputation wound with BMP9 stimulates regeneration of a synovial joint that forms an articulation with the stump bone. Regenerated structures include a skeletal element lined with articular cartilage and a synovial cavity, and we demonstrate that this response requires the Prg4 gene. Combining BMP2 and BMP9 treatments in sequence stimulates the regeneration of bone and joint. These studies provide evidence that treatment of growth factors can be used to engineer a regeneration response from a non-regenerating amputation wound.
| S-EPMC6363752 | biostudies-literature
Project description:BackgroundThe purpose of this study was to perform a cost-utility analysis to compare revision amputation and replantation treatment of finger amputation injuries across a spectrum of injury scenarios.MethodsThe study was conducted from the societal perspective. Decision tree models were created for the reference case (two-finger amputation injury) and seven additional injury scenarios for comparison. Inputs included cost, quality of life, and probability of each health state. A Web-based time trade-off survey was created to determine quality-adjusted life-years for health states; 685 nationally representative adult community members were invited to participate in the survey. Overall cost and quality-adjusted life-years for revision amputation and replantation were calculated for each decision tree. An incremental cost-effectiveness ratio was calculated if a treatment was more costly but more effective.ResultsThe authors had a 64 percent response rate (n = 437). Replantation treatment had greater costs and quality-adjusted life-years compared with revision amputation in all injury scenarios. Replantation of single-digit injuries had the highest incremental cost-effectiveness ratio ($136,400 per quality-adjusted life-year gained). Replantation of three- and four-digit amputation injuries had relatively low cost-to-benefit ratios ($27,100 and $23,800 per quality-adjusted life-year, respectively). Replantation for distal thumb amputation had a relatively low incremental cost-effectiveness ratio ($26,300 per quality-adjusted life-year) compared with replantation of nonthumb distal amputations ($60,200 per quality-adjusted life-year).ConclusionsThe relative cost per quality-adjusted life-year gained with replantation treatment varied greatly among the injury scenarios. Situations in which indications for replantation are debated had higher cost per quality-adjusted life-year gained. This study highlights variability in value for replantation among different injury scenarios.
| S-EPMC4154255 | biostudies-literature
Project description:Digit regrowth following amputation injury proximal to the first phalangeal joint is not a property of mammalian wound healing. However, the regenerative potential observed in the MRL mouse invites a reexamination of this rule. In this study, healing was assessed in three mouse strains after amputation midway through the second phalangeal bone. Three distinct outcomes were observed though evidence for regrowth was observed only in the MRL mouse. Here, a blastema-like structure was seen along with apparent chondrogenesis, consistent with a histological profile of a regenerative response to injury. Analysis of trichrome staining and basement membrane changes, proliferation and apoptosis indicated that these processes contributed to the formation of new digit tissue. On the other hand, SW and B6 digits did not show evidence of growth with little mesenchymal BrdU incorporation or phosphorylation of H3.
| S-EPMC3645464 | biostudies-literature
Project description:Replantation is a prime indication for distal digital amputation, as it helps restore hand aesthetics and functions; however, venous anastomosis is often not feasible. Previous studies used systemic anticoagulation in distal digital artery only anastomosis replantation surgery to improve replantation success rate, however, which yielded limited level of clinical evidence. This study aimed to compare controlled continuous heparinization (CCH) and intermittent bolus heparinization (IBH) for surgical outcome and clinical variables after single distal digital artery only anastomosis replantation surgery.A single-institution, retrospective cohort study was performed. Out of 324 patients who underwent digital replantation surgery, we focused the study for the Zone I and II single distal digital amputation patients excluding confounding factors. Sixty-one patients were included in this study and underwent artery-only anastomosis replantation surgery with postoperative CCH (34 patients) or IBH (27 patients) protocols. The CCH group targeted activated partial thromboplastin time (aPTT) at 51 to 70 seconds, monitoring aPTT levels every eight hours and administering 100 mg of aspirin per day. The IBH group received 300 mg of aspirin per day and underwent IBH (12,500 U). Both groups received intravenous prostaglandin E1 drips (10 μg). To verify the factors affecting the success rate of the heparin protocol, patient factors, clinical factors, and operative factors were extracted from the medical records. Statistical analysis with inverse probability of treatment weights propensity score methods compared treatment outcomes and clinical variables.The CCH group's replantation success rate was higher (91.17% vs 59.25%), and the transfusion rate was increased (P = 0.032). However, the significant decrease in hemoglobin levels (>15%) did not differ between the groups (P = 0.108). Multivariable logistic regression analysis with potent univariate variables (P < .10) revealed that CCH was a statistically significant variable in replantation success rate (P = 0.004). Neither the major bleeding complications nor the significant decrease in patients' platelet levels were observed in both groups.Our study suggests that CCH after artery-only anastomosis replantation surgery in Zone I and II distal digital replantation is a safe method to improve the replantation success rate and may provide a guideline for use of the anticoagulation method following artery-only anastomosis distal digital replantation surgery.
| S-EPMC4937911 | biostudies-literature
Project description:Regeneration is classically demonstrated in mammals using mice digit tip. In this study, we compared different amputation plans and show that distally amputated digits regrow with morphology close to normal but fail to regrow the fat pad. Proximally amputated digits do not regrow the phalangeal bone, but the remaining structures (nail, skin and connective tissue), all with intrinsic regenerative capacity, re-establishing integrity indistinguishably in distally and proximally amputated digits. Thus, we suggest that the bone growth promoted by signals and progenitor cells not removed by distal amputations is responsible for the re-establishment of a drastically different final morphology after distal or proximal digit tip amputations. Despite challenging the use of mouse digit tip as a model system for limb regeneration in mammals, these findings evidence a main role of bone growth in digit tip regeneration and suggest that mechanisms that promote joint structures formation should be the main goal of regenerative medicine for limb and digit regrowth.
| S-EPMC6609708 | biostudies-literature
Project description:ImportanceTraumatic digit amputation is the most common type of amputation injury, but the cost-effectiveness of its treatments is unknown.ObjectiveTo assess the cost-effectiveness of finger replantation compared with revision amputation.Design, setting, and participantsThis economic evaluation was conducted using data from the Finger Replantation and Amputation Challenges in Assessing Impairment, Satisfaction, and Effectiveness (FRANCHISE), a retrospective, multicenter cohort study at 19 centers in the United States and Asia that enrolled participants from August 1, 2016, to April 12, 2018. Model variables were based on the FRANCHISE database, Centers for Medicare & Medicaid Services, and published literature. A total of 257 participants with unilateral traumatic finger amputations treated with revision amputation or replantation distal to the metacarpophalangeal joint and at least 1 year of follow-up after treatment were included in the analysis.ExposuresRevision amputation or replantation of traumatic finger amputations.Main outcomes and measuresMain outcome measures were quality-adjusted life-years (QALYs), total costs (in US dollars), and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold of $100 000 per QALY was used to assess cost-effectiveness.ResultsOf the 257 study participants (mean [SD] age, 46.7 [15.9] years; 221 [86.0%] male), 178 underwent finger replantation and 79 underwent revision amputation. In a base case of a 46.7-year-old patient, replantation was associated with QALY gains of 0.30 (95% credible interval [CrI], -0.72 to 1.38) for single-finger (not thumb), 0.39 (95% CrI, -1.00 to 1.90) for thumb, 1.69 (95% CrI, -0.13 to 3.76) for multifinger excluding thumb, and 1.27 (95% CrI, -2.21 to 5.04) for multifinger including thumb injury patterns. Corresponding ICERs for replantation compared with revision amputation were $99 157 per QALY for single-finger (not thumb), $66 278 per QALY for thumb, $18 388 per QALY for multifinger excluding thumb, and $21 528 per QALY for multifinger including thumb injury patterns. Sensitivity analysis revealed that age at time of injury, life expectancy, postinjury utility, wages, and time off work for recovery had the strongest associations with cost-effectiveness. Probabilistic sensitivity analysis revealed the following chances of replantation being cost-effective: 47% in single-finger (not thumb), 52% in thumb, 78% in multifinger excluding thumb, and 64% in multifinger including thumb injury patterns.Conclusions and relevanceWith proper patient selection, replantation of all finger amputation patterns, whether single-finger or multifinger injuries, may be cost-effective compared with revision amputation. Multifinger replantations had a higher probability of being cost-effective than single-finger replantations. Cost-effectiveness may depend on injury pattern and patient factors and thus appears to be important for consideration when patients and surgeons are deciding whether to replant or amputate.
| S-EPMC6902751 | biostudies-literature
Project description:Regeneration of amputated structures is severely limited in humans and mice, with complete regeneration restricted to the distal portion of the terminal phalanx (P3). Here, we investigate the dynamic tissue repair response of the second phalangeal element (P2) post amputation in the adult mouse, and show that the repair response of the amputated bone is similar to the proximal P2 bone fragment in fracture healing. The regeneration-incompetent P2 amputation response is characterized by periosteal endochondral ossification resulting in the deposition of new trabecular bone, corresponding to a significant increase in bone volume; however, this response is not associated with bone lengthening. We show that cells of the periosteum respond to amputation and fracture by contributing both chondrocytes and osteoblasts to the endochondral ossification response. Based on our studies, we suggest that the amputation response represents an attempt at regeneration that ultimately fails due to the lack of a distal organizing influence that is present in fracture healing.
| S-EPMC4857751 | biostudies-literature
Project description:BackgroundLittle is known about the association between the quality of trauma care and management of nonfatal injuries. The authors used emergency department wait times as a proxy for hospital structure, process, and availability of on-call surgeons with microsurgical skills. They evaluated the association between average hospital emergency department wait times and likelihood of undergoing digit replantation for patients with traumatic amputation digit injuries. The authors hypothesized that hospitals with shorter emergency department wait times were associated with higher odds of replantation.MethodsUsing the 2007 to 2012 National Trauma Data Bank, the authors' final sample included 12,126 patients. Regression modeling was used to first determine factors that were associated with longer emergency department wait times among patients with digit amputation injuries. Second, the authors examined the association between emergency department wait times for this population at a hospital level and replantation after all types of digit amputation and after complicated thumb amputation injuries only.ResultsFor patients with simple and complicated thumb amputation injuries, and patients with complicated thumb amputation injuries only, longer emergency department wait times were associated with lower odds of replantation. In addition, being minority and having no insurance were associated with longer emergency department wait times; teaching hospitals were associated with shorter emergency department wait times; and finally, for patients with complicated thumb amputation injuries only, there was no association between patients' minority or insurance status and replantation.ConclusionVariation in emergency department wait time and its effects on treatment of traumatic digit amputation may reflect maldistribution of hand or plastic surgeons with the required microsurgical skills among trauma centers across the United States.Clinical question/level of evidenceTherapeutic, III.
| S-EPMC5300165 | biostudies-literature