Computational pathology in 2030: a Delphi study forecasting the role of AI in pathology within the next decade.

BACKGROUND: Artificial intelligence (AI) is rapidly fuelling a fundamental transformation in the practice of pathology. However, clinical integration remains challenging, with no AI algorithms to date in routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience. METHODS: Perspectives were solicited using the Delphi method from 24 subject matter experts between December 2020 and February 2021 regarding the anticipated role of AI in pathology by the year 2030. The study consisted of three consecutive rounds: 1) an open-ended, free response questionnaire generating a list of survey items; 2) a Likert-scale survey scored by experts and analysed for consensus; and 3) a repeat survey of items not reaching consensus to obtain further expert consensus. FINDINGS: Consensus opinions were reached on 141 of 180 survey items (78.3%). Experts agreed that AI would be routinely and impactfully used within AP laboratory and pathologist clinical workflows by 2030. High consensus was reached on 100 items across nine categories encompassing the impact of AI on (1) pathology key performance indicators (KPIs) and (2) the pathology workforce and specific tasks performed by (3) pathologists and (4) AP lab technicians, as well as (5) specific AI applications and their likelihood of routine use by 2030, (6) AI's role in integrated diagnostics, (7) pathology tasks likely to be fully automated using AI, and (8) regulatory/legal and (9) ethical aspects of AI integration in pathology. INTERPRETATION: This systematic consensus study details the expected short-to-mid-term impact of AI on pathology practice. These findings provide timely and relevant information regarding future care delivery in pathology and raise key practical, ethical, and legal challenges that must be addressed prior to AI's successful clinical implementation. FUNDING: No specific funding was provided for this study.

Fused Cells between Human-Adipose-Derived Mesenchymal Stem Cells and Monocytes Keep Stemness Properties and Acquire High Mobility.

Human-adipose-derived mesenchymal stem cells (hADMSCs) are multipotent stem cells which have become of great interest in stem-cell therapy due to their less invasive isolation. However, they have limited migration and short lifespans. Therefore, understanding the mechanisms by which these cells could migrate is of critical importance for regenerative medicine. Methods: Looking for novel alternatives, herein, hADMSCs were isolated from adipose tissue and co-cultured with human monocytes ex vivo. Results: A new fused hybrid entity, a foam hybrid cell (FHC), which was CD90+CD14+, resulted from this co-culture and was observed to have enhanced motility, proliferation, immunomodulation properties, and maintained stemness features. Conclusions: Our study demonstrates the generation of a new hybrid cellular population that could provide migration advantages to MSCs, while at the same time maintaining stemness properties.

Effects of Ischemic Preconditioning and C1 Esterase Inhibitor Administration following Ischemia-Reperfusion Injury in a Rat Skin Flap Model.

BACKGROUND: Ischemia-reperfusion (I/R) injury is a serious condition that can affect the success rate of microsurgical reconstructions of ischemic amputated limbs and complex tissue defects requiring free tissue transfers. The purpose of this study was to evaluate the effects of ischemic preconditioning (IPC) and C1 esterase inhibitor (C1-Inh) intravenous administration following I/R injury in a rat skin flap model. METHODS: Superficial caudal epigastric skin flaps (3 cm × 7 cm) were performed on 50 Wistar rats that were randomly divided into five groups. Ischemia was not induced in the control group. All other flaps underwent 8 hours of ischemia prior to revascularization: I/R control group (8-hour ischemia), IPC group (preconditioning protocol + 8-hour ischemia), C1-Inh group (8-hour ischemia + C1-Inh), and IPC + C1-Inh group (preconditioning protocol + 8-hour ischemia + C1-Inh). Survival areas were macroscopically assessed after 1 week of surgery, and histopathological and biochemical evaluations were also measured. RESULTS: There were no significant differences in flap survival between the treatment groups that were suffering 8 hours of ischemia and the control group. A significant increase in neovascularization and lower edema formation were observed in the IPC group compared with that in the I/R group. Biochemical parameters did not show any significant differences. CONCLUSION: Intravenous administration of C1-Inh did not significantly modulate I/R-related damage in this experimental model, but further research is needed. On the other hand, IPC reduces tissue damage and improves neovascularization, confirming its potential protective effects in skin flaps following I/R injury.

Outcomes of DIEP Flap and Fluorescent Angiography: A Randomized Controlled Clinical Trial.

BACKGROUND: Breast reconstruction with the deep inferior epigastric perforator (DIEP) flap can be associated with complications such as fat necrosis. The authors' objective was to assess the safety and efficacy of fluorescent angiography with indocyanine green to reduce fat necrosis. METHODS: The authors designed a parallel, randomized, controlled clinical trial for unilateral breast reconstruction. The poorly vascularized tissues of the DIEP flap were removed based on a clinical evaluation in group 1 and based on angiographic criteria in group 2. The authors recorded the flap dimensions, perfusion in terms of fluorescence intensity, complications, reoperations, and BREAST-Q questionnaire scores for both groups. RESULTS: The study included a total of 51 patients. The flaps showed no size differences after the tissue was excised. The flaps of group 2 presented higher perfusion rates (p = 0.001). The incidence of fat necrosis was 59.3 percent in group 1 and 8.3 percent in group 2 (p = 0.001). Four cases of partial necrosis were recorded in group 1 (18.2 percent) compared with none in group 2 (0 percent) (p = 0.131). Four patients underwent reoperation in group 1 (14.8 percent) compared with none in group 2 (0 percent) (p = 0.113). The patients in group 2 reported higher scores in all domains of the BREAST-Q. CONCLUSIONS: Fluorescent angiography with indocyanine green significantly reduced the incidence of fat necrosis without diminishing the flaps' dimensions. The perfusion rates were significantly higher and the patients reported significantly greater satisfaction and quality of life. Fluorescent angiography with indocyanine green may be considered a safe and effective tool to enhance the outcomes of breast reconstruction with the DIEP flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Effect of Cold Preservation on Chronic Rejection in a Rat Hindlimb Transplantation Model.

BACKGROUND: Previous studies on solid organ transplantation have shown that cold ischemia contributes to the development of chronic allograft vasculopathy. The authors evaluated the effect of cold ischemia on the development of chronic rejection in vascularized composite allotransplantation. METHODS: Thirty rat hindlimbs were transplanted and divided into two experimental groups: immediate transplantation and transplantation after 7 hours of cold ischemia. The animals received daily low-dose immunosuppression with cyclosporine A for 2 months. Intimal proliferation, arterial permeability rate, leukocyte infiltration, and tissue fibrosis were assessed. The CD3, CD4, CD8, CD20, and CD68 cells per microscopic field (200×) were counted, and C4d deposition was investigated. Cytokine RNA analysis was performed to measure tumor necrosis factor-α, interleukin-6, and interleukin-10 levels. RESULTS: Significant differences were found in the intimal proliferation and arterial permeability rate between the two groups (p = 0.004). The arterial permeability rate worsened in the most distal and small vessels (p = 0.047). The numbers of CD3, CD8, CD20, and CD68 were also statistically higher in the cold ischemia group (p < 0.05, all levels). A trend toward significance was observed with C4d deposition (p = 0.059). No differences were found in the RNA of cytokines. CONCLUSIONS: An association between cold ischemia and chronic rejection was observed in experimental vascularized composite allotransplantation. Chronic rejection intensity and distal progression were significantly related with cold ischemia. The leukocyte infiltrates in vascularized composite allotransplantation components were a rejection marker; however, their exact implication in monitoring and their relation with cold ischemia are yet to be clarified.

Safety of salvaging impending flap congestion in breast reconstruction by venous supercharging of the cephalic vein.

Autologous flap breast reconstruction is an established technique that carries a risk of vascular failure. We evaluated the safety of salvaging impending venous congestion by using the cephalic vein for supercharging autologous abdominal flaps. Our main outcome measures were flap survival, triggering or impairing lymphedema as measured by the physician or reported by the patient, and scar severity as measured by the Vancouver scar scale. We were able to save 100% of the flaps, but could not find any statistical association with or without increased lymphedema before and after the procedure. One patient reported that lymphedema worsened. The patients accepted the scars (mean Vancouver scar scale score, 5.7). In sum, using the cephalic vein to improve venous drainage of autologous breast reconstruction was safe and did not trigger or impair lymphedema, but scarring in the upper arm was unavoidable.

Factors influencing acute rejection of human hand allografts: a systematic review.

Acute rejection (AR) of human hand allografts (HHAs) may carry a risk of graft loss and leads to the need for immunosuppressive treatment. The literature on HHAs was reviewed to determine and evaluate the factors that trigger AR of HHAs. Clinical case reports of hand allograft transplantation published between 1999 and 2011 in English, French, or German were reviewed systematically. The number of AR episodes was the main outcome measure. Sixty-eight episodes of AR were described in 28 recipients. Calcineurin inhibitor-based maintenance regimens were associated with significantly fewer AR episodes than non-calcineurin inhibitor-based regimens (mean 1.9 vs 3.2; P = 0.018). In recipients who experienced cytomegalovirus infection, the mean number of episodes of AR was 4, whereas in those who did not experience cytomegalovirus infection it was 2.25 (P = 0.024). The planning of hand allograft transplantation should take these factors into account to minimize the risk of AR.

Outcomes with respect to disabilities of the upper limb after hand allograft transplantation: a systematic review.

The aim of this work is to compare disabilities of the upper limb before and after hand allograft transplantation (HAT), and to describe the side effects of immunosuppressive (IS) agents given to recipients of hand allografts. Clinical cases of HAT published between 1999 and 2011 in English, French, or German were reviewed systematically, with emphasis on comparing disabilities of the arm, shoulder and hand (DASH) scores before and after transplantation. Duration of ischemia, extent of amputation, and time since amputation were evaluated for their effect on intrinsic musculature function. Infectious, metabolic, and oncological complications because of IS therapy were recorded. Twenty-eight patients were reported in 56 clinical manuscripts. Among these patients, disabilities of the upper limb dropped by a mean of 27.6 (±19.04) points on the DASH score after HAT (P = 0.005). Lower DASH scores (P = 0.036) were recorded after secondary surgery on hand allografts. The presence of intrinsic muscle function was observed in 57% of the recipients. Duration of ischemia, extent of transplantation, and time since amputation were not associated statistically with the return of intrinsic musculature function. Three grafts were lost to follow-up because of noncompliance with immunosuppression, rejection, and arterial thrombosis, respectively. Fifty-two complications caused by IS agents were reported, and they were successfully managed medically or surgically. HAT recipients showed notable functional gains, but most complications resulted from the IS protocols.