Adherence to embryo transfer guidelines in favorable-prognosis patients aged less than 35 years using autologous oocytes and in recipients using donor oocytes: a Society for Assisted Reproductive Technology Clinic Outcome Reporting System study.

OBJECTIVE: To measure the consequences of nonadherence with the 2013 American Society for Reproductive Medicine elective single embryo transfer (eSET) guidelines for favorable-prognosis patients. DESIGN: Retrospective cohort. SETTING: In vitro fertilization clinics. PATIENT(S): A total of 28,311 fresh autologous, 2,500 frozen-thawed autologous, and 3,534 fresh oocyte-donor in vitro fertilization cycles in 2014-2016 at Society for Assisted Reproductive Technology-reporting centers. INTERVENTION(S): Patients aged <35 years or using donors aged <35 years underwent first blastocyst transfer. MAIN OUTCOME MEASURE(S): Singleton birth rate, gestational age at delivery, and birth weight were compared between the eSET and non-eSET groups using the chi-square or Fisher's exact test or t-tests. RESULT(S): Among fresh transfers, 15,643 (55%) underwent eSET. Live births after non-eSETs were less likely singletons (38.0% vs. 96.5%; adjusted relative risk [aRR], 0.56) and more likely complicated by preterm delivery (55.0% vs. 20.1%; aRR, 2.39) and low birth weight (<2,500 g) (40.1% vs. 10.6%; aRR, 3.4) compared with those after eSET. Among frozen-thawed transfers, 1,439 (58%) underwent eSET. Live births after non-eSETs were less likely singletons (41.9% vs. 95.2%; aRR, 0.69; 95% confidence interval, 0.66-0.73) and more likely complicated by preterm delivery (56.4% vs. 19.5%; aRR, 2.6; 95% confidence interval, 2.2-3.1) and low birth weight (38.0% vs. 8.9%; aRR, 3.9) compared with those after eSET. Among fresh donor oocyte transfers, 1,946 (55%) underwent eSET. Live births after non-eSETs were less likely singletons (31.3% vs. 97.3%; aRR, 0.48) and more likely complicated by preterm delivery (61.1% vs. 25.7%; aRR, 2.09) and low birth weight (44.3% vs. 11.7%; aRR, 3.39) compared with those after eSET. CONCLUSION(S): Nonadherence with transfer guidelines was associated with dramatically increased multiple pregnancies, preterm births, and low birth weights.

Oncological Safety of Autologous Fat Grafting in Breast Reconstruction after Mastectomy for cancer: A case-control study.

OBJECTIVE: The use of autologous fat grafting in the context of breast reconstruction is still a matter of controversy. The objective of this study was to compare the local relapse rate in women who had a fat grafting session in the context of breast reconstruction after breast cancer management, to those who had breast reconstruction without fat grafting. METHODS: We performed a retrospective, monocentric, case-control study from January 2007 to December 2017 in our hospital. The cases included women who underwent breast reconstruction with autologous fat grafting and controls, undergoing breast reconstruction without fat grafting. We compared survival and local recurrence between the two groups. RESULTS: 412 women were included: 109 (26.5%) in the lipofilling group and 303 women (73.5%) in the "no lipofilling" group. In the overall study population, lipofilling did not appear to be a predictive factor for recurrence, HR = 1.39 [0.63 - 3.06], p = 0.41; or a predictive factor for overall survival, HR = 0.84 [0.23 - 3.02], p = 0.79, or for distant metastases, HR = 1.10 [0.43 - 2.79], p = 0.84. In contrast, in the subgroup of women treated for invasive cancer, the multivariate analysis showed that lipofilling in this context was an independent predictive factor for local recurrence (HR= 5.06 [1.97 - 10.6], p = 0.04). CONCLUSION: we found an increased risk of local recurrence after lipofilling in women who were managed for invasive breast cancer. This suggests that special consideration should be given to women who have had invasive breast cancer before lipofilling.

Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience.

We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020). Data on patient characteristics, manufacturing parameters, and manufacturing outcomes were collected from manufacturing batch records and entered into a secure database. Overall, 88% (36/41) of PolyTreg products met release criteria and 83% (34/41) of products were successfully infused into patients. Of the 7 not infused, 5 failed release criteria, and 2 were not infused because the patient became ineligible due to a change in clinical status. The median fold expansion over the 14-day manufacturing process was 434.8 -fold (range 29.8-2,232), resulting in a median post-expansion cell count of 1,841 x 106 (range 56.9-16,179 x 106). The main correlate of post-expansion cell number was starting cell number, which positively correlates with absolute circulating Treg cell count. Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production.

Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway.

PURPOSE: Is it possible to eliminate metastasised chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells from ovarian cortex fragments by inhibition of Aurora B/C kinases (AURKB/C) without compromising ovarian tissue or follicles? METHODS: Human ovarian cortex tissue with experimentally induced tumour foci of CML, AML and primary cells of AML patients were exposed to a 24h treatment with 1 µM GSK1070916, an AURKB/C inhibitor, to eliminate malignant cells by invoking mitotic catastrophe. After treatment, the inhibitor was removed, followed by an additional culture period of 6 days to allow any remaining tumour cells to form new foci. Ovarian tissue integrity after treatment was analysed by four different assays. Appropriate controls were included in all experiments. RESULTS: Foci of metastasised CML and AML cells in ovarian cortex tissue were severely affected by a 24h ex vivo treatment with an AURKB/C inhibitor, leading to the formation of multi-nuclear syncytia and large-scale apoptosis. Ovarian tissue morphology and viability was not compromised by the treatment, as no significant difference was observed regarding the percentage of morphologically normal follicles, follicular viability, glucose uptake or in vitro growth of small follicles between ovarian cortex treated with 1 µM GSK1070916 and the control. CONCLUSION: Purging of CML/AML metastases in ovarian cortex is possible by targeting the Mitotic Catastrophe Signalling Pathway using GSK1070916 without affecting the ovarian tissue. This provides a therapeutic strategy to prevent reintroduction of leukaemia and enhances safety of autotransplantation in leukaemia patients currently considered at high risk for ovarian involvement.

Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis: Recommendations of the National Multiple Sclerosis Society.

Importance: Autologous hematopoietic stem cell transplant (AHSCT) for multiple sclerosis has gained increasing interest in recent years. Despite the availability of many US Food and Drug Administration-approved disease-modifying therapies, some patients do not respond adequately and others may have very early aggressive disease that prompts consideration of alternative, highly effective, long-lasting therapy. The National Medical Advisory Committee of the National Multiple Sclerosis Society has reviewed recent literature on AHSCT for the purpose of making recommendations about its use based on current knowledge, as well as pointing out areas of controversy and issues requiring further research. Observations: Studies on AHSCT have repeatedly demonstrated high efficacy and a durable outcome in people with relapsing multiple sclerosis. Recent studies have shown considerable improvement in the safety of the procedure, with much lower mortality rates than were reported earlier. Consensus is emerging about the characteristics of the best candidates for the procedure. Questions remain about the ideal protocol, particularly about the best conditioning regimen to be used to kill immune cells. Larger randomized clinical trials are needed to address the question of whether AHSCT has advantages over the most efficacious disease-modifying agents currently available. One such trial (Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis [BEAT-MS) is currently in progress. Conclusions and Relevance: The National Multiple Sclerosis Society believes that AHSCT may be a useful treatment option for people with relapsing multiple sclerosis who demonstrate substantial breakthrough disease activity (ie, new inflammatory central nervous system lesions and/or clinical relapses) despite treatment with high-efficacy disease-modifying therapy or have contraindications to high-efficacy disease-modifying therapies. The best candidates are likely people younger than 50 years with shorter durations of disease (<10 years). The procedure should only be performed at centers with substantial experience and expertise. Ideally, recipients of the procedure should be entered into a single database, and further research is needed to establish ideal cell mobilization and immune-conditioning regimens.

To Transplant or Not to Transplant During the SARS-CoV-2 Pandemic? That Is the Question.

The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high-dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS-CoV-2 infection.

Validation of the UK myeloma research alliance risk profile, a new clinical prediction model for outcome in patients with newly diagnosed multiple myeloma not eligible for autologous stem cell transplantation; a population-based study from the Danish national multiple myeloma registry.

In 2019 the UK Myeloma Research Alliance introduced the Myeloma Risk Profile (MRP) for prediction of outcome in patients with newly diagnosed multiple myeloma (MM), ineligible for autologous stem cell transplantation. To validate the MRP in a population-based setting we performed a study of the entire cohort of transplant ineligible MM patients above 65 years in the Danish National MM Registry. Our data confirmed the value of the MRP. In a cohort of 1,377 patients, the MRP score separated patients into three distinct risk-groups with an observed hazard ratio of 2.91 for early death in high-risk versus low-risk patients.

Acceleration of Skin Wound-Healing Reactions by Autologous Micrograft Tissue Suspension.

Background and objectives: Skin grafting is a method usually used in reconstructive surgery to accelerate skin regeneration. This method results frequently in unexpected scar formations. We previously showed that cutaneous wound-healing in normal mice is accelerated by a micrograft (MG) technique. Presently, clinical trials have been performed utilizing this technology; however, the driving mechanisms behind the beneficial effects of this approach remain unclear. In the present study, we focused on five major tissue reactions in wound-healing, namely, regeneration, migration, granulation, neovascularization and contraction. Methods: Morphometrical analysis was performed using tissue samples from the dorsal wounds of mice. Granulation tissue formation, neovascularization and epithelial healing were examined. Results: The wound area correlated well with granulation sizes and neovascularization densities in the granulation tissue. Vascular distribution analysis in the granulation tissue indicated that neovessels extended and reached the subepidermal area in the MG group but was only halfway developed in the control group. Moreover, epithelialization with regeneration and migration was augmented by MG. Myofibroblast is a known machinery for wound contraction that uses α-smooth muscle actin filaments. Their distribution in the granulation tissue was primarily found beneath the regenerated epithelium and was significantly progressed in the MG group. Conclusions: These findings indicated that MG accelerated a series of wound-healing reactions and could be useful for treating intractable wounds in clinical situations.

Disparities in Access to Autologous Breast Reconstruction.

Background and objectives: This study aimed to determine if age, race, region, insurance, and comorbidities affect the type of breast reconstruction that patients receive. Materials and methods: This analysis used the Florida Inpatient Discharge Dataset from 1 January 2013 to 30 September 2017, which contains deidentified patient-level administrative data from all acute care hospitals in the state of Florida. We included female patients, diagnosed with breast cancer, who underwent mastectomy and a subsequent breast reconstruction. We performed an χ2 test and logistic regression in this analysis. Results: On the multivariable analysis, we found that age, race, patient region, insurance payer, and Elixhauser score were all variables that significantly affected the type of reconstruction that patients received. Our results show that African American (odds ratio (OR): 0.68, 95%CI: 0.58-0.78, p < 0.001) and Hispanic or Latino (OR: 0.82, 95%CI: 0.72-0.93, p = 0.003) patients have significantly lower odds of receiving implant reconstruction when compared to white patients. Patients with Medicare (OR: 1.57, 95%CI: 1.33-1.86, p < 0.001) had significantly higher odds and patients with Medicaid (OR: 0.61, 95%CI: 0.51-0.74, p < 0.001) had significantly lower odds of getting autologous reconstruction when compared to patients with commercial insurance. Conclusions: Our study demonstrated that, in the state of Florida over the past years, variables, such as race, region, insurance, and comorbidities, play an important role in choosing the reconstruction modality. More efforts are needed to eradicate disparities and give all patients, despite their race, insurance payer, or region, equal access to health care.

Outcomes in patients with aggressive B-cell non-Hodgkin lymphoma after intensive frontline treatment failure.

BACKGROUND: Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. METHODS: Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. RESULTS: In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse <12 months from completion of first-line therapy) experienced inferior median PFS (2.8 vs 23 months; P < .001) and OS (6 months vs not reached; P < .001) compared with patients with late treatment failure. Although the 17% of patients with early failure who achieved a complete response to second-line immunochemotherapy experienced prolonged survival, this outcome could not be predicted by clinicopathologic features at the start of second-line immunochemotherapy. CONCLUSIONS: Patients with early treatment failure after intensive first-line immunochemotherapy experience poor outcomes after receiving standard second-line immunochemotherapy. The use of standard-of-care or experimental therapies currently available in the third-line setting and beyond should be investigated in the second-line setting for these patients.

Comparison of Immune Reconstitution After Allogeneic Versus Autologous Stem Cell Transplantation in 182 Pediatric Recipients.

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for children with a variety of malignant and nonmalignant conditions. However, even if immune reconstitution after HSCT has been studied extensively, until now, data on the comparison of immune reconstitution after autologous versus allogeneic HSCT are scarce, but might provide important clinical implications. We examined immune reconstitution (T cells, B cells, and NK cells) at defined timepoints in 147 children who received 182 HSCTs. Differences in the time course of immune reconstitution were analyzed in autologous versus allogeneic HSCT. We identified a quicker immune reconstitution in the T-cell compartment, especially in the CD4 and naive subset after autologous HSCT, whereas recipients of allogeneic transplants showed a higher TCRgd proportion. B-cell reconstitution showed a delayed immune reconstitution after allogeneic HSCT in the first 2 years after HSCT. However, a reconstitution of all lymphocyte subsets after HSCT could be achieved in all patients. Children undergoing an HSCT show a different pattern of immune reconstitution in the allogeneic and autologous setting. This might influence the outcome and should affect the clinical handling of infectious prophylaxis and revaccinations.

Medial patellofemoral ligament reconstruction in children: A comparative randomized short-term study of fascia lata allograft and gracilis tendon autograft reconstruction.

BACKGROUND: Many surgical procedures have been described to treat recurrent patellar dislocation, but none of these techniques has been successful in all patients. The goal of the study was to evaluate the results of medial patellofemoral ligament reconstruction in children. Two operative procedures were evaluated; a fascia lata allograft and an autologous gracilis graft. METHODS: Forty-four children (27 girls and 17 boys) between 13 and 17 years of age with unilateral recurrent patellar dislocation underwent medial patellofemoral ligament (MPFL) reconstruction. Patients were operated in two orthopedic centers. The 1st group contained 22 patients and surgery was performed using a fascia lata allograft. In the 2nd group of patients which also contained 22 children and autologous gracilis graft was used. The mean age of the patients was 14.9 years and the mean follow-up was 24 months. Preoperatively, all patients were evaluated clinically (Kujala score questionnaire) and radiologically. The same evaluation was used 18 to 30 months postoperatively to estimate the results of our treatment. RESULTS: In 1st group of children operated with cadaver allografts, the Kujala score significantly improved from 73.91 points preoperatively to 94.50 points postoperatively (P < .001). The average duration of operating procedure was 1 hour and 35 minutes. As shown by subjective symptoms, the results in 95% of patients were rated as good or very good. All children returned to full activity. Similar results were obtained in patients in 2nd group, where MPFL was reconstructed with ipsilateral gracilis tendon. Kujala score increased from 70.77 points preoperatively to 94.32 postoperatively (P < .001). Our results were estimated as good or very good in 93% of patients. All patients that were operated returned to full activity. However, median duration of operation was longer and lasted 1 hour and 55 minutes. CONCLUSIONS: Both techniques were effective in the short-term (18-30 months) in treatment of recurrent patellar dislocation. The use of cadaver allograft spares the hamstring muscles and reduces the time of surgery. Therefore, such study appears to be useful because it provides valuable information that would help to guide treatment of this condition in children. Level of evidence II-2.

Back to Basics: Autologous Tissue: 1.5 www.aornjournal.org/content/cme.

Perioperative personnel manage autologous tissue when they care for patients undergoing procedures requiring the use of bone, soft tissue, or other autologous tissue to repair or replace defects. Use of autologous tissue can minimize the risk of rejection, disease transfer, and infection compared with the use of artificial materials. There are important steps to follow when handling autologous tissue to ensure it is safe for replantation and does not become contaminated. This Back to Basics article provides strategies for managing some types of autologous tissue, including bone flaps, parathyroid tissue, skin grafts, and veins. Tissue management strategies include creating strict documentation policies, standardizing processes and communication, and implementing routine audits to assess compliance.

Bone augmentation using autogenous bone versus biomaterial in the posterior region of atrophic mandibles: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to answer the PICO question: "Do patients who have received bone grafts with bone substitute (biomaterials) present bone gain (before implant installation), complications, and implant survival rates similar to autogenous grafts when used in the posterior mandible region?". DATA: This review followed the PRISMA statement and has been registered at PROSPERO (CRD42016048471). Studies published in English, randomized controlled and/or prospective clinical trials with at least 10 patients, and studies that compared grafts with bone substitutes to autogenous bone grafts (split-mouth design) were included. SOURCES: An electronic search and a manual search were conducted in PubMed/MEDLINE, Scopus, and Cochrane databases up to April 2018. STUDY SELECTION: Our initial search yielded 640 articles; we selected four articles that met the inclusion criteria. All selected studies used a split-mouth design. RESULTS: Our analysis revealed no significant difference between the biomaterial and autogenous groups in terms of bone gain (P = 0.11; mean difference [MD]: 0.59; 95% confidence interval [CI]: -0.13-1.31) or complication rate (P = 0.72; risk ratio [RR]: 1.25; 95% CI: 0.37-4.23). Sixty-six implants were installed in the biomaterial group and 63 in the autogenous group; these showed no significant difference in implant survival rate (P = 0.50; RR: 1.57; 95% CI: 0.43-5.81). CONCLUSION: We conclude that biomaterials or autogenous bone are indicated for the reconstruction of the posterior mandibular atrophic region, without lowering implant survival.

Management of Multiple Myeloma.

The most recent NCCN Guidelines for Multiple Myeloma include a ranking of the many treatment options for various settings as "preferred," "other," and "useful in certain circumstances." For patients eligible for autologous stem cell transplant (ASCT), the preferred regimen remains bortezomib/lenalidomide/dexamethasone (category 1) or bortezomib/cyclophosphamide/dexamethasone. Upfront ASCT also remains a preferred strategy for patients who are transplant-eligible, despite highly effective newer agents such as induction therapy. Double (tandem) ASCT may benefit patients with high-risk cytogenetics, such as 17p deletion. Lenalidomide maintenance is the standard posttransplant approach and results in improved progression-free and overall survivals. For relapsed disease, a host of new agents have been shown to improve outcomes, mostly in combination with bortezomib or lenalidomide, but their selection depends largely on response and tolerability to prior therapies.

Evaluating the Impact of Resident Participation and the July Effect on Outcomes in Autologous Breast Reconstruction.

OBJECTIVE: Although resident involvement in surgical procedures is critical for training, it may be associated with increased morbidity, particularly early in the academic year-a concept dubbed the "July effect." Assessments of such phenomena within the field of plastic surgery have been both limited and inconclusive. We sought to investigate the impact of resident participation and academic quarter on outcomes for autologous breast reconstruction. METHODS: All autologous breast reconstruction cases after mastectomy were gathered from the 2005-2012 American College of Surgeons National Surgical Quality Improvement Program database. Multivariable logistic regression models were constructed to investigate the association between resident involvement and the first academic quarter (Q1 = July-September) with 30-day morbidity (odds ratios [ORs] with 95% confidence intervals). Medical and surgical complications, median operation time, and length of stay (LOS) were also compared. RESULTS: Overall, 2527 cases were identified. Cases with residents (n = 1467) were not associated with increased 30-day morbidity (OR, 1.20; 0.95-1.52) when compared with those without (n = 1060), although complications including transfusion (OR, 2.08; 1.39-3.13) and return to the operating room (OR, 1.46; 1.11-1.93) were more frequently observed in resident cases. Operation time and LOS were greater in cases with resident involvement.In cases with residents, there was decreased morbidity in Q1 (n = 343) when compared with later quarters (n = 1124; OR, 0.67; 0.48-0.92). Specifically, transfusion (OR, 0.52; 0.29-0.95), return to operating room (OR, 0.64; 0.41-0.98), and surgical site infection (OR, 0.37; 0.18-0.75) occurred less often during Q1. No differences in median operation time or LOS were observed within this subgroup. CONCLUSIONS: Our study reveals that resident involvement in autologous breast reconstruction is not associated with increased morbidity and offers no evidence for a July effect. Notably, our results suggest that resident cases performed earlier in the academic year, when surgical attendings may offer more surveillance and oversight, is associated with decreased morbidity.

The US Direct-to-Consumer Marketplace for Autologous Stem Cell Interventions.

Hundreds of businesses and clinics in the United States are engaged in direct-to-consumer marketing of unproven and unlicensed stem cell-based interventions. This essay provides an overview of this marketplace, examines advertising techniques companies use to draw clients and legitimate marketing claims, and summarizes the roles the Food and Drug Administration (FDA) and other agencies are supposed to play in regulating the direct-to-consumer marketplace for stem cell interventions. The essay also reviews federal regulations, describes how many businesses selling purported "stem cell treatments" appear to violate these standards, and considers ethical issues and harms associated with widespread promotion of unapproved stem cell products.